ARHGEF16, also called Ephexin-4 and originally cloned as the neuroblastoma candidate gene NBR, is a Dbl-family Rho guanine nucleotide exchange factor built from a long regulatory N-terminus, a tandem DH-PH catalytic cassette, an SH3 domain and a C-terminal PDZ-binding motif. Its direct substrate is the Rho-family GTPase RhoG: the purified DH-PH cassette loads GTP onto RhoG and not onto Rac1, and in cells the protein raises RhoG-GTP without raising Rac1, Cdc42 or RhoA. That makes it the exception within its own family, whose other four members - Ephexin-1 (NGEF), Ephexin-2 (ARHGEF19), Ephexin-3 (ARHGEF5) and Ephexin-5 (ARHGEF15) - are RhoA exchange factors. Rac1 is activated downstream of ARHGEF16 indirectly: active RhoG recruits its effector ELMO2 together with the Rac exchange factor DOCK4 to the plasma membrane, and the resulting complex assembles with the receptor tyrosine kinase EPHA2 at the tips of cortactin-rich protrusions. Through that route ARHGEF16 supports ligand-independent cell migration and invasion toward EGF, suppresses anoikis via RhoG-dependent PI3K and Akt signalling, and contributes to cortical organisation during mitosis. In mouse, Ephexin-4 also promotes engulfment of apoptotic cells in cooperation with ELMO1. The exchange activity is held off by two independent autoinhibitory modes, an N-terminal intermolecular one in which the SH3 domain of one molecule occludes the N-terminal region of another, and a C-terminal one involving the PDZ-binding motif; ELMO proteins relieve the first and PDZ-domain proteins such as TAX1BP3 relieve the second, so the same partners that act downstream of the GTPase also license the reaction that produces it. Upstream, EPHA2 phosphorylated on Ser897 recruits ARHGEF16, placing it on the ligand-independent, Akt-driven arm of Eph receptor signalling that is associated with tumour progression.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005085 guanyl-nucleotide exchange factor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Family-level propagation of DH-domain guanine-nucleotide exchange activity from the ephexin clade. The WITH/FROM carries three ephexin siblings (NGEF/Ephexin-1 Q8N5V2, ARHGEF5/Ephexin-3 Q12774, ARHGEF15/Ephexin-5 O94989), a mouse donor, and ARHGEF16's own accession Q5VV41, which is expected because ARHGEF16's own IDA from PMID:20679435 is one of the descendant evidences behind the IBD. Reason: Exchange activity is genuinely shared across the ephexin family, and the target's own experimental annotation legitimately appears among the donors rather than inflating them. Worth stating plainly, though, that this IBA is correct only because the term is coarse: three of the four protein donors are RhoA GEFs, and ARHGEF16 is the one family member that does not touch RhoA. At the granularity GO used to offer (GO:0005089 Rho GEF activity, now merged into GO:0005085) this propagation would have transferred a specificity the target demonstrably lacks. See ARHGEF16-bioinformatics/RESULTS.md section 1. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN002656129 · ephexin-family ancestral node SUPPORTS TRANSFER Node at which DH-domain exchange activity was placed. UniProtKB:Q8N5V2 · NGEF / Ephexin-1 SUPPORTS TRANSFER RhoA GEF with experimental support; shares the DH-PH cassette. UniProtKB:Q12774 · ARHGEF5 / Ephexin-3 (TIM) SUPPORTS TRANSFER RhoA GEF; shares the DH-PH cassette. UniProtKB:O94989 · ARHGEF15 / Ephexin-5 SUPPORTS TRANSFER RhoA GEF; shares the DH-PH cassette. UniProtKB:Q5VV41 · ARHGEF16 itself SUPPORTS TRANSFER The target's own IDA (PMID:20679435) is one of the descendant evidences behind the IBD; expected, not circular. MGI:MGI:3045246 · mouse donor UNRESOLVED MGI identifier not resolved to a gene symbol in this review; recorded rather than guessed. Supporting Evidence: PMID:30445756 however, Ephexin4 displays GEF activity for RhoG, rather than for RhoA file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md All four general parents are childless by |
| GO:0005085 guanyl-nucleotide exchange factor activity | IDA PMID:20679435 Ephexin4 and EphA2 mediate cell migration through a RhoG-dep... | ACCEPT | Summary: Direct measurement: the purified DH-PH cassette of Ephexin4 catalyses nucleotide exchange on RhoG, and does not exchange on Rac1. This is the protein's defining activity and the anchor for the whole review. Reason: In vitro exchange on purified protein, with the negative arm run in the same experiment. The has_input extension records RHOG because GO itself cannot: GO:0005089 Rho guanyl-nucleotide exchange factor activity was merged into GO:0005085, GO:0005085 has no is_a children on the GO API, OLS4 or QuickGO, and the merge was confirmed on two independent services (ARHGEF16-bioinformatics/RESULTS.md section 1). Supporting Evidence: PMID:20679435 Although the DH-PH domain of Ephexin4 did not exchange nucleotide on Rac1, it possessed GEF activity of RhoG in vitro PMID:20679435 Flag-tagged Ephexin4 expressed in HEK293T cells bound to the nucleotide-free forms of RhoG and Rac1 but not to those of RhoA and Cdc42 |
| GO:0005085 guanyl-nucleotide exchange factor activity | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro signature mapping from IPR000219 (DH domain) and IPR047271 (Ephexin-like), both of which ARHGEF16 carries. Reason: The domain assignment is correct and the term it maps to is the correct general one. The structural check agrees independently: ARHGEF16 retains 50-70% of the GTPase-contacting DH surface across six solved DH-GTPase complexes, inside the range of bona fide Dbl-family GEFs and far above the non-DH out-group. That is confirmatory only, and is not evidence that the protein is active - full-length Ephexin4 is autoinhibited and quiet until de-repressed, so an intact exchange surface and no measurable activity are compatible states. The activity is known because it was measured on purified protein, not because the residues are there. Supporting Evidence: file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Each anchor's own GEF scores 1.00, which is the internal check that the SIFTS |
| GO:0005096 GTPase activator activity | IDA PMID:21139582 The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, ... | MODIFY | Summary: A GTPase-activating-protein molecular function annotated to a guanine-nucleotide exchange factor. PMID:21139582 measured nucleotide exchange, not GTP hydrolysis: 'In vitro kinetic analysis confirmed that recombinant ARHGEF16 activates Cdc42'. GO:0005096 is the GAP term - 'Binds to and increases the activity of a GTPase, an enzyme that catalyzes the hydrolysis of GTP' - whose synonyms are Rho GAP activity, Rac GAP activity and Ras GAP activity, and whose alternative ids are the merged substrate-specific GAP terms. A GAP accelerates hydrolysis and switches the GTPase off; a GEF loads GTP and switches it on. The word 'activates' has been routed to the activator term. Reason: This is a term-choice error, not a doubt about the experiment or the gene: the paper's own title calls ARHGEF16 a GEF, the protein has no GAP domain (UniProt lists DH, PH and SH3 only; the InterPro signatures are IPR000219 and IPR047271), and the same curator on the same paper chose the correct BP term GO:0032489. The trap is that GO:0090630 'activation of GTPase activity', which this gene also carries and which IS correct, has a name that reads like the GAP molecular function while its definition is exchange-based ('replacement of GDP by GTP'). Both definitions were pinned on two services. The replacement is GO:0005085, with CDC42 as has_input, which preserves everything the experiment showed. The blast radius is the reason to fix it rather than note it: QuickGO returns 83 annotations across 81 taxa carrying UniProtKB:Q5VV41 in WITH/FROM for GO:0005096, all by Ensembl Compara IEA (GO_REF:0000107) or ISO (GO_REF:0000119), and mouse Arhgef16 - which has no experimental annotation of its own - carries it twice. Proposed replacements: guanyl-nucleotide exchange factor activity Supporting Evidence: PMID:21139582 In vitro kinetic analysis confirmed that recombinant ARHGEF16 activates Cdc42 and this was increased by the addition of recombinant Tip-1 and E6. PMID:20679435 Although the DH-PH domain of Ephexin4 did not exchange nucleotide on Rac1, it possessed GEF activity of RhoG in vitro file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md The single human row has been projected to 83 orthologs in 81 species. |
| GO:0005515 protein binding | IPI PMID:15161933 Comprehensive proteomic analysis of interphase and mitotic 1... | MODIFY | Summary: Recovery of ARHGEF16 as a YWHAZ/14-3-3 zeta interactor in a 14-3-3 proteomic screen. Reason: The partner is a 14-3-3 protein and GO:0071889 '14-3-3 protein binding' is active and describes the interaction exactly, so the uninformative generic term should be replaced rather than removed. The assignment is consistent with the protein's phosphorylation state: UniProt maps ten phosphosites on ARHGEF16 (S6, S41, S107, S174, S191, S208, S227, S230, S240 and T226), and 14-3-3 capture is phospho-dependent. Seven GO:0005515 rows across five references report this one binding mode. Proposed replacements: 14-3-3 protein binding |
| GO:0005515 protein binding | IPI PMID:15778465 Targeted proteomic analysis of 14-3-3 sigma, a p53 effector ... | MODIFY | Summary: Recovery of ARHGEF16 as a SFN/14-3-3 sigma interactor in a 14-3-3 proteomic screen. Reason: The partner is a 14-3-3 protein and GO:0071889 '14-3-3 protein binding' is active and describes the interaction exactly, so the uninformative generic term should be replaced rather than removed. The assignment is consistent with the protein's phosphorylation state: UniProt maps ten phosphosites on ARHGEF16 (S6, S41, S107, S174, S191, S208, S227, S230, S240 and T226), and 14-3-3 capture is phospho-dependent. Seven GO:0005515 rows across five references report this one binding mode. Proposed replacements: 14-3-3 protein binding |
| GO:0005515 protein binding | IPI PMID:20679435 Ephexin4 and EphA2 mediate cell migration through a RhoG-dep... | KEEP AS NON CORE | Summary: Interaction with ELMO2, the RhoG effector. In PMID:20679435 active RhoG recruits ELMO2 together with the Rac GEF Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions, which is how Rac1 gets activated downstream of a GEF that does not itself touch Rac1. Reason: A real, mechanistically important interaction, but GO:0005515 says nothing about it and there is no informative molecular-function term for 'binds the effector of the GTPase I load'. ELMO proteins are on both sides of this protein's biology - downstream effector here, and upstream de-repressor in PMID:28667327, where Elmo1 competes the SH3 domain off the N20 region and makes Ephexin4 accessible to RhoG - so the interaction is better captured in core_functions and in the notes than by replacing this row. Supporting Evidence: PMID:28667327 Elmo1 relieves the steric hindrance of Ephexin4 generated by the intermolecular interaction of the SH3 domain and makes Ephexin4 more accessible to RhoG. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Binary yeast two-hybrid interaction with TFG (unreviewed TrEMBL entry Q05BK6, 366 aa) from a proteome-scale human interactome map. Reason: A systematic binary screen result with no follow-up and no mechanistic account for this gene. TFG carries no PDZ domain, so unlike the bulk of this gene's GO:0005515 rows it cannot be attributed to the C-terminal PDZ-binding motif, and there is no more informative molecular-function term to move it to. Kept because it is a real measurement, marked non-core because nothing in the ARHGEF16 literature builds on it. Note that this row and the Q92734 row in the same reference are the same protein under two accessions: Q05BK6 is the unreviewed TrEMBL entry (Q05BK6_HUMAN, 366 aa, from EMBL clone BC041600) and Q92734 is the reviewed Swiss-Prot entry (TFG_HUMAN, 400 aa). Both carry gene name TFG and a single PB1 domain; neither is Tensin-3, which is Q68CZ2 and lists no secondary accessions. GOA therefore counts one binding partner twice here, which is a duplicate-partner artefact rather than two findings. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Binary yeast two-hybrid interaction with MAPK1IP1L from a proteome-scale human interactome map. Reason: A systematic binary screen result with no follow-up and no mechanistic account for this gene. MAPK1IP1L carries no PDZ domain, so unlike the bulk of this gene's GO:0005515 rows it cannot be attributed to the C-terminal PDZ-binding motif, and there is no more informative molecular-function term to move it to. Kept because it is a real measurement, marked non-core because nothing in the ARHGEF16 literature builds on it. |
| GO:0005515 protein binding | IPI PMID:25416956 A proteome-scale map of the human interactome network. | KEEP AS NON CORE | Summary: Binary yeast two-hybrid interaction with TFG (reviewed Swiss-Prot entry Q92734, 400 aa) from a proteome-scale human interactome map. Reason: A systematic binary screen result with no follow-up and no mechanistic account for this gene. TFG carries no PDZ domain, so unlike the bulk of this gene's GO:0005515 rows it cannot be attributed to the C-terminal PDZ-binding motif, and there is no more informative molecular-function term to move it to. Kept because it is a real measurement, marked non-core because nothing in the ARHGEF16 literature builds on it. Note that this row and the Q92734 row in the same reference are the same protein under two accessions: Q05BK6 is the unreviewed TrEMBL entry (Q05BK6_HUMAN, 366 aa, from EMBL clone BC041600) and Q92734 is the reviewed Swiss-Prot entry (TFG_HUMAN, 400 aa). Both carry gene name TFG and a single PB1 domain; neither is Tensin-3, which is Q68CZ2 and lists no secondary accessions. GOA therefore counts one binding partner twice here, which is a duplicate-partner artefact rather than two findings. |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | MODIFY | Summary: Recovery of ARHGEF16 as a YWHAZ/14-3-3 zeta interactor in a 14-3-3 proteomic screen. Reason: The partner is a 14-3-3 protein and GO:0071889 '14-3-3 protein binding' is active and describes the interaction exactly, so the uninformative generic term should be replaced rather than removed. The assignment is consistent with the protein's phosphorylation state: UniProt maps ten phosphosites on ARHGEF16 (S6, S41, S107, S174, S191, S208, S227, S230, S240 and T226), and 14-3-3 capture is phospho-dependent. Seven GO:0005515 rows across five references report this one binding mode. This row comes from an affinity-purification dataset, the same method class as the GO:0045296 cadherin row that this review marks over-annotated, so the different verdict needs saying. Two things separate them. The retyped term here names the partner class actually recovered (a 14-3-3 protein), whereas GO:0045296 asserts contact with cadherin specifically, which an E-cadherin complex pulldown cannot distinguish from capture via the eleven junctional PDZ scaffolds ARHGEF16 does bind. And the 14-3-3 result is replicated across five independent references and three partners with an independent mechanistic basis in the protein's ten mapped phosphosites, whereas the cadherin row is a single dataset. The generic-to-specific retyping is therefore a change of label on a reproduced observation, not a new claim of directness. Proposed replacements: 14-3-3 protein binding |
| GO:0005515 protein binding | IPI PMID:30126976 Proteome-wide analysis of phospho-regulated PDZ domain inter... | MODIFY | Summary: Interaction with the PDZ-domain protein DLG1, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:30126976 Proteome-wide analysis of phospho-regulated PDZ domain inter... | MODIFY | Summary: Interaction with the PDZ-domain protein SCRIB, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:32203420 Systems analysis of RhoGEF and RhoGAP regulatory proteins re... | MODIFY | Summary: Interaction with the PDZ-domain protein DLG1, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:32203420 Systems analysis of RhoGEF and RhoGAP regulatory proteins re... | MODIFY | Summary: Interaction with the PDZ-domain protein SNTB2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:32203420 Systems analysis of RhoGEF and RhoGAP regulatory proteins re... | MODIFY | Summary: Interaction with the PDZ-domain protein SCRIB, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary yeast two-hybrid interaction with HNRNPH1 from a proteome-scale human interactome map. Reason: A systematic binary screen result with no follow-up and no mechanistic account for this gene. HNRNPH1 carries no PDZ domain, so unlike the bulk of this gene's GO:0005515 rows it cannot be attributed to the C-terminal PDZ-binding motif, and there is no more informative molecular-function term to move it to. Kept because it is a real measurement, marked non-core because nothing in the ARHGEF16 literature builds on it. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary yeast two-hybrid interaction with LASP1 isoform 2 from a proteome-scale human interactome map. Reason: A systematic binary screen result with no follow-up and no mechanistic account for this gene. LASP1 isoform 2 carries no PDZ domain, so unlike the bulk of this gene's GO:0005515 rows it cannot be attributed to the C-terminal PDZ-binding motif, and there is no more informative molecular-function term to move it to. Kept because it is a real measurement, marked non-core because nothing in the ARHGEF16 literature builds on it. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary yeast two-hybrid interaction with BOLL isoform 4 from a proteome-scale human interactome map. Reason: A systematic binary screen result with no follow-up and no mechanistic account for this gene. BOLL isoform 4 carries no PDZ domain, so unlike the bulk of this gene's GO:0005515 rows it cannot be attributed to the C-terminal PDZ-binding motif, and there is no more informative molecular-function term to move it to. Kept because it is a real measurement, marked non-core because nothing in the ARHGEF16 literature builds on it. |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: Binary yeast two-hybrid interaction with MAGED1 from a proteome-scale human interactome map. Reason: A systematic binary screen result with no follow-up and no mechanistic account for this gene. MAGED1 carries no PDZ domain, so unlike the bulk of this gene's GO:0005515 rows it cannot be attributed to the C-terminal PDZ-binding motif, and there is no more informative molecular-function term to move it to. Kept because it is a real measurement, marked non-core because nothing in the ARHGEF16 literature builds on it. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MODIFY | Summary: Recovery of ARHGEF16 as a YWHAZ/14-3-3 zeta interactor in a 14-3-3 proteomic screen. Reason: The partner is a 14-3-3 protein and GO:0071889 '14-3-3 protein binding' is active and describes the interaction exactly, so the uninformative generic term should be replaced rather than removed. The assignment is consistent with the protein's phosphorylation state: UniProt maps ten phosphosites on ARHGEF16 (S6, S41, S107, S174, S191, S208, S227, S230, S240 and T226), and 14-3-3 capture is phospho-dependent. Seven GO:0005515 rows across five references report this one binding mode. This row comes from an affinity-purification dataset, the same method class as the GO:0045296 cadherin row that this review marks over-annotated, so the different verdict needs saying. Two things separate them. The retyped term here names the partner class actually recovered (a 14-3-3 protein), whereas GO:0045296 asserts contact with cadherin specifically, which an E-cadherin complex pulldown cannot distinguish from capture via the eleven junctional PDZ scaffolds ARHGEF16 does bind. And the 14-3-3 result is replicated across five independent references and three partners with an independent mechanistic basis in the protein's ten mapped phosphosites, whereas the cadherin row is a single dataset. The generic-to-specific retyping is therefore a change of label on a reproduced observation, not a new claim of directness. Proposed replacements: 14-3-3 protein binding |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein SDCBP/syntenin-1, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein PDZD2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein MPDZ, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein TJP3/ZO-3, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein APBA3, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein DLG4/PSD-95, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein TJP1/ZO-1, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein PTPN13, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein DLG1, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein SNTB2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein IL16, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein SCRIB, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein NHERF2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein DLG2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein PDZK1, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein MAGI3, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein MAST2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein PDZRN4, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein PREX2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein MAGI2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein NHERF4, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein LNX2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein PATJ, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein LNX1, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein DLG5, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein PARD3, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein PARD3B, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein DLG3, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein MAGI1, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein APBA2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein GRIP2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein SDCBP2/syntenin-2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein PDZD7, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein WHRN, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein TJP2/ZO-2, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein GRIP1, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: Interaction with the PDZ-domain protein USH1C/harmonin, reported by a screen that assays PDZ-domain binding. Reason: ARHGEF16 ends in ...ETDV, a canonical class I PDZ-binding motif that UniProt annotates as MOTIF 707-709, and every partner in this group carries PDZ domains. Forty-two GO:0005515 rows across three references therefore report one C-terminal binding determinant measured many times, not forty-two independent findings. GO:0030165 PDZ domain binding says what the interaction is and is already on this gene from PMID:21139582 (TAX1BP3), so the generic term should be replaced rather than kept. The replacement is not decoration: PMID:33597305 shows that association of PDZ proteins with this motif relieves one of the two autoinhibitory modes that hold the DH domain shut, which makes PDZ binding a regulator of the gene's own catalytic activity rather than an incidental contact. The partition is checked rather than asserted, in both directions: pdz_partner_check.py reads this review and fetches each partner live from UniProt, confirming that all 38 partners on the PDZ side carry a PDZ domain - 147 between them, including TAX1BP3, the one partner GOA itself already types GO:0030165 - and that none of the 11 accessions outside that set does. Those 11 accessions are 10 distinct proteins: TFG appears twice, as the reviewed Q92734 and the unreviewed Q05BK6. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:33597305 phosphorylation of a conserved tyrosine residue in its N-terminal inhibitory domain and association of PDZ proteins with its C-terminal PDZ-binding motif may respectively relieve the two autoinhibitory modes in Ephexin4 file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Recovery of ARHGEF16 as a SFN/14-3-3 sigma interactor in a 14-3-3 proteomic screen. Reason: The partner is a 14-3-3 protein and GO:0071889 '14-3-3 protein binding' is active and describes the interaction exactly, so the uninformative generic term should be replaced rather than removed. The assignment is consistent with the protein's phosphorylation state: UniProt maps ten phosphosites on ARHGEF16 (S6, S41, S107, S174, S191, S208, S227, S230, S240 and T226), and 14-3-3 capture is phospho-dependent. Seven GO:0005515 rows across five references report this one binding mode. Proposed replacements: 14-3-3 protein binding |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Recovery of ARHGEF16 as a YWHAE/14-3-3 epsilon interactor in a 14-3-3 proteomic screen. Reason: The partner is a 14-3-3 protein and GO:0071889 '14-3-3 protein binding' is active and describes the interaction exactly, so the uninformative generic term should be replaced rather than removed. The assignment is consistent with the protein's phosphorylation state: UniProt maps ten phosphosites on ARHGEF16 (S6, S41, S107, S174, S191, S208, S227, S230, S240 and T226), and 14-3-3 capture is phospho-dependent. Seven GO:0005515 rows across five references report this one binding mode. Proposed replacements: 14-3-3 protein binding |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | MODIFY | Summary: Recovery of ARHGEF16 as a YWHAZ/14-3-3 zeta interactor in a 14-3-3 proteomic screen. Reason: The partner is a 14-3-3 protein and GO:0071889 '14-3-3 protein binding' is active and describes the interaction exactly, so the uninformative generic term should be replaced rather than removed. The assignment is consistent with the protein's phosphorylation state: UniProt maps ten phosphosites on ARHGEF16 (S6, S41, S107, S174, S191, S208, S227, S230, S240 and T226), and 14-3-3 capture is phospho-dependent. Seven GO:0005515 rows across five references report this one binding mode. Proposed replacements: 14-3-3 protein binding |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasm, from the UniProt subcellular-location keyword mapping. Reason: Consistent with UniProt's own SUBCELLULAR LOCATION statement (Cytoplasm, ECO:0000305) and with the cell biology: Ephexin4 acts on RhoG at the plasma membrane from a cytoplasmic pool, and PMID:39675713 reports that its knockdown reduces RhoG localization to the plasma membrane. |
| GO:0005829 cytosol | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Cytosol, from an ARBA machine-learning rule. Reason: Compatible with the cytoplasmic assignment and with the two Reactome TAS rows for the same term, but it is a rule-based inference with no ARHGEF16-specific observation behind it. No experiment in this gene's literature localises the protein, which is recorded as a CC knowledge gap. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-205039 | KEEP AS NON CORE | Summary: Cytosol, asserted by Reactome reaction R-HSA-205039. Reason: The cytosol term itself is uncontroversial and is kept. Its provenance is not: R-HSA-205039 places ARHGEF16 in a DefinedSet of Dbl-family GEFs whose catalysed output is Rac and Cdc42, and PMID:20679435 specifically failed to detect activation of those GTPases by Ephexin4 - the supporting quote on this row is the negative for Rac and Cdc42, measured in that paper against Dock180, Zizimin1 or Ephexin1 as the positive control. Membership in that set is by DH domain rather than by measured specificity - it also contains TIAM1 and TIAM2 (Rac-only), FGD1-FGD4 and ITSN1 (Cdc42-only) and SOS1, SOS2 and RASGRF2 (Ras), across 52-54 protein participants. Only the cytosol term reaches GOA, so this is recorded as provenance rather than as a GO error, but a reader of the Reactome page is told this protein activates a GTPase it does not. Supporting Evidence: PMID:20679435 we could observe no obvious increase in the activities of Rac1 and Cdc42 in HEK293T cells by expression of Ephexin4 |
| GO:0005829 cytosol | TAS Reactome:R-HSA-419166 | KEEP AS NON CORE | Summary: Cytosol, asserted by Reactome reaction R-HSA-419166. Reason: The cytosol term itself is uncontroversial and is kept. Its provenance is not: R-HSA-419166 places ARHGEF16 in a DefinedSet of Dbl-family GEFs whose catalysed output is RhoA, RhoB and RhoC, and PMID:20679435 specifically failed to detect activation of those GTPases by Ephexin4 - the supporting quote on this row is the negative for RhoA, RhoB and RhoC, measured in that paper against Dock180, Zizimin1 or Ephexin1 as the positive control. Membership in that set is by DH domain rather than by measured specificity - it also contains TIAM1 and TIAM2 (Rac-only), FGD1-FGD4 and ITSN1 (Cdc42-only) and SOS1, SOS2 and RASGRF2 (Ras), across 52-54 protein participants. Only the cytosol term reaches GOA, so this is recorded as provenance rather than as a GO error, but a reader of the Reactome page is told this protein activates a GTPase it does not. Supporting Evidence: PMID:20679435 we could not detect the increase in RhoA activity in cells expressing Ephexin4 |
| GO:0030165 PDZ domain binding | IPI PMID:21139582 The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, ... | ACCEPT | Summary: Interaction with the PDZ protein TAX1BP3 (TIP-1) through ARHGEF16's carboxy-terminal PDZ-binding motif (UniProt MOTIF 707-709). Reason: Correctly typed - the partner supplies the PDZ domain and ARHGEF16 supplies the motif, which is the direction GO:0030165 encodes. It is also the mechanistically loaded one of this gene's binding rows: PMID:33597305 shows that association of PDZ proteins with this motif relieves the C-terminal of the two autoinhibitory modes that impede RhoG access, so PDZ binding regulates the gene's own exchange activity. This row is the replacement target for the 42 generic protein-binding rows contributed by PDZ-domain screens. Supporting Evidence: PMID:21139582 Tax-interacting-protein 1 was shown to interact with ARHGEF16 by its carboxyl PDZ binding motif. PMID:33597305 The crystal structures of partially and fully autoinhibited Ephexin4 reveal that the complete autoinhibition requires both N- and C-terminal inhibitory modes, which can operate independently to impede Ras homolog family member G (RhoG) access. |
| GO:0030971 receptor tyrosine kinase binding | IPI PMID:20679435 Ephexin4 and EphA2 mediate cell migration through a RhoG-dep... | ACCEPT | Summary: Interaction with the receptor tyrosine kinase EPHA2, the receptor that recruits Ephexin4 and places its exchange activity downstream of EphA2 signalling. Reason: Informative as a molecular function and central rather than incidental: UniProt annotates region 275-481 as 'Required for RHOG activation and mediates interaction with EPHA2', and PMID:23772378 shows the interaction is tuned by EphA2 phosphorylation on Ser897, with the S897A mutant abolishing EphA2/Ephexin4-mediated RhoG activation. Supporting Evidence: PMID:23772378 S897 phosphorylation of EphA2 strengthens the interaction between EphA2 and Ephexin4, a guanine nucleotide exchange factor for the small GTPase RhoG. |
| GO:0031267 small GTPase binding | IPI PMID:20679435 Ephexin4 and EphA2 mediate cell migration through a RhoG-dep... | KEEP AS NON CORE | Summary: Binding to nucleotide-free RAC1. PMID:20679435 reports that Ephexin4 binds the nucleotide-free forms of both RhoG and Rac1, but exchanges nucleotide only on RhoG. Reason: The binding is real and measured, and it is deliberately not the substrate relationship: the same figure shows no exchange on Rac1 in vitro and no increase in cellular Rac1-GTP, with Dock180 as the positive control. Rac1 is activated downstream, but by Dock4 recruited via RhoG-ELMO2. GO:0031267 small GTPase binding is already the most specific term available - GO:0017048 Rho GTPase binding was merged into it, confirmed on two services - so there is nothing to modify to, and the binding-without-exchange distinction is inexpressible. Supporting Evidence: PMID:20679435 Flag-tagged Ephexin4 expressed in HEK293T cells bound to the nucleotide-free forms of RhoG and Rac1 but not to those of RhoA and Cdc42 PMID:20679435 we could observe no obvious increase in the activities of Rac1 and Cdc42 in HEK293T cells by expression of Ephexin4 |
| GO:0031267 small GTPase binding | IPI PMID:20679435 Ephexin4 and EphA2 mediate cell migration through a RhoG-dep... | ACCEPT | Summary: Binding to RHOG, the GTPase on which Ephexin4 catalyses exchange. Reason: This is the substrate interaction, and it is the same measurement that underlies the GEF activity row: binding to nucleotide-free RhoG is the mechanistic signature of an exchange factor engaging its GTPase. Kept as core. GO:0031267 is as specific as the ontology now permits, since GO:0017048 Rho GTPase binding was merged into it. The three GO:0031267 rows on this gene deliberately do not share an action, and the divergence is the point rather than an oversight: the rows differ by WITH/FROM partner, and binding RhoG (the substrate that gets exchanged) is a different claim from binding Rac1 (bound but never exchanged, with the negative measured in the same figure) or Cdc42 (bound only with HPV16 E6 present, and not bound at all in the other primary paper). Collapsing them to one action would either promote two non-substrate contacts to core or demote the substrate. Supporting Evidence: PMID:20679435 Although the DH-PH domain of Ephexin4 did not exchange nucleotide on Rac1, it possessed GEF activity of RhoG in vitro |
| GO:0031267 small GTPase binding | IPI PMID:21139582 The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, ... | KEEP AS NON CORE | Summary: Co-immunoprecipitation of CDC42 with ARHGEF16, reported in the presence of high-risk HPV E6. Reason: An experimental annotation from a curator with the full text, and not removed. It does, however, conflict with the other primary paper on this protein: PMID:20679435 reports that Ephexin4 does not bind nucleotide-free Cdc42 in HEK293T cells. The two reconcile on conditionality rather than on error - every positive Cdc42 result in PMID:21139582 is conditioned on Tip-1 and/or HPV16 E6 being present, and the negative experiments were done without either. Demoted to non-core on that basis: a cofactor-dependent interaction in an HPV context, not the protein's constitutive partner. This row is also where the deep-research record went wrong, and instructively so: the affinage report names Cdc42 as this protein's core biochemical activity and does not mention RhoG anywhere, because its retrieval is keyed on the symbol ARHGEF16 while every RhoG paper is titled Ephexin4. Its trust gates were clean, which certified the six citations it returned and said nothing about the twenty it did not. Supporting Evidence: PMID:21139582 Cdc42 was co-immunoprecipitated by ARHGEF16 in the presence of high-risk HPV E6. PMID:20679435 Flag-tagged Ephexin4 expressed in HEK293T cells bound to the nucleotide-free forms of RhoG and Rac1 but not to those of RhoA and Cdc42 file:human/ARHGEF16/ARHGEF16-deep-research-affinage.md Its core biochemical activity is direct guanine nucleotide exchange on Cdc42, demonstrated by in vitro kinetic analysis of recombinant protein |
| GO:0032489 regulation of Cdc42 protein signal transduction | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Phylogenetic propagation of the Cdc42-signalling process term from node PTN002656172, whose only protein donor is ARHGEF16's own accession. Reason: Not circular in the schema's sense - the target's own IDA is a legitimate descendant evidence behind an IBD - but the honest reading is that this node's support is exactly as strong as that single experiment and no stronger, and that experiment is the contested, HPV-E6-conditioned Cdc42 arm. Unlike the GO:0005085 and GO:0032956 IBAs, which draw on three ephexin siblings each, no other family member contributes here. Kept as non-core rather than removed: the underlying IDA stands, and a propagation whose source is a real experimental annotation is not a propagation failure. Propagation Review Root cause: SOURCE WEAK OR INFERRED Failure modes: SOURCE EVIDENCE WEAK Sources checked: PANTHER:PTN002656172 · ARHGEF16-proximal node SUPPORTS TRANSFER Node placement itself is not disputed; the evidence under it is thin. UniProtKB:Q5VV41 · ARHGEF16 itself SUPPORTS TRANSFER The target's own IDA from PMID:21139582; expected in WITH/FROM, and the only protein donor at this node. |
| GO:0032489 regulation of Cdc42 protein signal transduction | IDA PMID:21139582 The HPV16 E6 binding protein Tip-1 interacts with ARHGEF16, ... | KEEP AS NON CORE | Summary: Regulation of Cdc42 signalling, from the in vitro exchange kinetics and cellular Cdc42-GTP measurements of PMID:21139582. Reason: The process term is a defensible reading of that paper and is kept; the molecular-function row from the same paper is the one that is wrong (see the GO:0005096 entry). It is demoted because the Cdc42 arm is contested and conditional: PMID:20679435 found no increase in cellular Cdc42-GTP on Ephexin4 expression, with Zizimin1 as the positive control, whereas every Cdc42-positive result in PMID:21139582 required Tip-1 or HPV16 E6. This is a genuine scientific disagreement between two experimental papers, not a curation error, and adjudicating it by REMOVE would overstate what either paper shows. Supporting Evidence: PMID:21139582 In vitro kinetic analysis confirmed that recombinant ARHGEF16 activates Cdc42 and this was increased by the addition of recombinant Tip-1 and E6. PMID:20679435 Dock180 and Zizimin1 were used as positive controls for activation of Rac1 and Cdc42, respectively |
| GO:0032956 regulation of actin cytoskeleton organization | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Family-level propagation of actin-cytoskeleton regulation from three ephexin siblings (ARHGEF15 O94989, ARHGEF5 Q12774, ARHGEF19 Q8IW93). No ARHGEF16-specific donor. Reason: Independently supported on this gene even though no donor is ARHGEF16: Ephexin4 drives cortactin-rich protrusions and EGF-directed migration through RhoG (PMID:20679435), and the de-repressed E295A mutant increases membrane ruffling (PMID:30445756). It is a downstream consequence of the exchange activity rather than the activity itself, so non-core. Propagation Review Root cause: NO FAILURE NON CORE Sources checked: PANTHER:PTN002656129 · ephexin-family ancestral node SUPPORTS TRANSFER Same node as the GO:0005085 IBA. UniProtKB:O94989 · ARHGEF15 / Ephexin-5 SUPPORTS TRANSFER Family donor. UniProtKB:Q12774 · ARHGEF5 / Ephexin-3 (TIM) SUPPORTS TRANSFER Family donor. UniProtKB:Q8IW93 · ARHGEF19 / Ephexin-2 SUPPORTS TRANSFER Family donor. |
| GO:0045296 cadherin binding | HDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | MARK AS OVER ANNOTATED | Summary: Cadherin binding from a quantitative E-cadherin interactome pulldown. Reason: HDA from an affinity pulldown of an E-cadherin complex, not a binary assay, so it reports co-purification rather than contact with cadherin. There is a parsimonious indirect route, and it is quantified rather than gestured at: eleven of the thirty-eight PDZ partners this gene binds through its C-terminal motif are junctional scaffolds - SCRIB, DLG1, MAGI1, MAGI2, MAGI3, PATJ, MPDZ, PARD3, TJP1, TJP2 and TJP3 - so capture in an E-cadherin complex is expected whether or not ARHGEF16 touches cadherin. Not removed, since the co-purification is a real observation and the curator had the full dataset; flagged as over-annotated because the term asserts a direct interaction the method cannot distinguish from an indirect one. Supporting Evidence: file:human/ARHGEF16/ARHGEF16-bioinformatics/RESULTS.md Every partner on the PDZ side carries at least one PDZ domain |
| GO:0060326 cell chemotaxis | IMP PMID:20679435 Ephexin4 and EphA2 mediate cell migration through a RhoG-dep... | ACCEPT | Summary: Chemotaxis: knockdown of Ephexin4 reduces migration of MDA-MB-231 breast cancer cells toward EGF, and the defect is rescued by wild-type Ephexin4 or by constitutively active RhoG but not by the DH-deleted mutant. Reason: Knockdown with two independent shRNAs plus rescue, and the rescue depends on the catalytic domain, which ties the process directly to the exchange activity rather than to a scaffolding role. Supporting Evidence: PMID:20679435 Although the DH-PH domain of Ephexin4 did not exchange nucleotide on Rac1, it possessed GEF activity of RhoG in vitro |
| GO:0090630 activation of GTPase activity | IMP PMID:20679435 Ephexin4 and EphA2 mediate cell migration through a RhoG-dep... | ACCEPT | Summary: The biological-process counterpart of the exchange activity, from RhoG activation measured on Ephexin4 knockdown and rescue. Reason: Correct, and worth flagging as correct because its name is the source of the error in this gene's record. GO:0090630 'activation of GTPase activity' reads like the GAP molecular function but is defined by exchange - 'Any process that initiates the activity of an inactive GTPase through the replacement of GDP by GTP', with synonyms Rho GTPase activation and Cdc42 GTPase activation. Both definitions were checked on the GO API and OLS4. This row is right; GO:0005096 on the same gene is not. Supporting Evidence: PMID:20679435 Although the DH-PH domain of Ephexin4 did not exchange nucleotide on Rac1, it possessed GEF activity of RhoG in vitro |
| GO:1903078 positive regulation of protein localization to plasma membrane | IMP PMID:20679435 Ephexin4 and EphA2 mediate cell migration through a RhoG-dep... | ACCEPT | Summary: Ephexin4-dependent recruitment of the ELMO2-Dock4 complex to the plasma membrane downstream of active RhoG, at the tips of cortactin-rich protrusions in migrating breast cancer cells. Reason: Knockdown-and-rescue evidence for a membrane-recruitment step that is the mechanistic link between this gene's exchange activity and the Rac1 activation it does not carry out itself. Independently corroborated fifteen years later in a different setting: Ephexin4 knockdown reduces RhoG localization to the plasma membrane in mitotic cells, rescued by wild-type and phospho-mimic S41E but not S41A. Supporting Evidence: PMID:39675713 The Ephexin4 knockdown caused chromosome misalignment and reduced the RhoG localization to the plasma membrane. |
| GO:2000811 negative regulation of anoikis | IMP PMID:21621533 Ephexin4 and EphA2 mediate resistance to anoikis through Rho... | NEW | Summary: Ephexin4 suppresses anoikis in human cells. Knockdown promotes anoikis in HeLa cells and lowers RhoG activity and Akt phosphorylation in suspension; a knockdown-rescue series shows that RhoG, PI3K and Akt activation are each required for the rescue. Corroborated independently through the receptor: the EphA2 S897A mutant, which cannot recruit Ephexin4, abolishes EphA2/Ephexin4-mediated RhoG activation and resistance to anoikis. Reason: Proposed rather than assumed, and it clears the bar the repository sets for NEW. The term is a regulation term, so acting upstream is what it means rather than a reason to withhold it, and the entity doing the work is ARHGEF16 itself: it loads GTP onto RhoG, and the rescue fails without that activation. The evidence is knockdown plus rescue in human cells, from two laboratories' papers a decade apart, and the second reaches the same conclusion through an orthogonal perturbation of the receptor rather than of ARHGEF16. GO currently carries nothing for this: QuickGO, queried by reference and species-blind across Q5VV41 and Q3U5C8, finds that of 26 papers naming this protein only two produced any GO annotation, and neither is an anoikis paper. No ancestor or descendant of GO:2000811 is already on this gene. Supporting Evidence: PMID:21621533 Knockdown of Ephexin4 promoted anoikis in HeLa cells, and experiments using a knockdown-rescue approach showed that activation of RhoG, phosphatidylinositol 3-kinase (PI3K), and Akt was required for the Ephexin4-mediated suppression of anoikis. PMID:23772378 S897A mutation of EphA2 abolished the EphA2/Ephexin4-mediated RhoG activation, promotion of cell migration, and resistance to anoikis. |
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Download this section (compressed HTML)Q: GO:0005096 GTPase activator activity is annotated by IDA to ARHGEF16 from PMID:21139582, a paper that measured nucleotide exchange. The protein has no GAP domain, and the same curator chose the correct process term from the same paper. Should the molecular function be retyped to GO:0005085 with CDC42 as has_input? The row has already been projected to 83 annotations across 81 taxa, including two on mouse Arhgef16, which has no experimental annotation of its own.
Suggested experts: BHF-UCL, GO Central, UniProt
Q: Every GO term that could state which GTPase a Rho-family regulator acts on has been merged away - the Rho/Rac/Ras GEF terms into GO:0005085, the substrate-specific GAP terms into GO:0005096, Rho GTPase binding into GO:0031267. For a family where one member's whole distinguishing feature is its substrate, is has_input on the activity row the intended replacement, and should it be expected rather than optional for GEF and GAP annotations?
Suggested experts: GO Central, GO ontology editors
Q: PMID:21139582 reports in vitro exchange on Cdc42, enhanced by Tip-1 and HPV16 E6, while PMID:20679435 reports no cellular Cdc42 activation and no binding to nucleotide-free Cdc42. Is the Cdc42 arm best curated as a cofactor-conditional activity, and if so should the GO:0032489 annotations carry an annotation extension naming the HPV16 E6 context rather than standing unqualified?
Suggested experts: BHF-UCL, GO Central
Q: PMID:39675713 shows that Ephexin4 knockdown prolongs metaphase, activates the spindle assembly checkpoint and causes chromosome misalignment, rescued by wild-type and S41E but not S41A. This review deliberately did not propose GO:0051310 metaphase chromosome alignment, because the entity that positions chromosomes is the spindle and kinetochore machinery and ARHGEF16 acts through cortical RhoG. Is there a regulation-level term that fits a cortical input to chromosome alignment, or is this a genuine expressivity gap?
Suggested experts: GO Central, cell-division curators
Q: Efferocytosis by Ephexin-4 is established for the mouse protein - murine cDNA NM_001112744 expressed in LR73 phagocytes, synergistic with ELMO1 and abolished without it - across three papers, yet mouse Arhgef16 has no experimental GO annotation at all. Should GO:0043277 apoptotic cell clearance be curated on mouse Arhgef16, from which it would then project to human by the same ISO route that currently projects the erroneous GAP term?
Suggested experts: MGI, GO Central
Q: Isoform Q5VV41-2 lacks residues 1-288, removing the entire N-terminal autoinhibitory region while retaining the exchange surface essentially intact (within 0.04 of the canonical at all six structural anchors tested). If the intermolecular autoinhibition model holds, this isoform should be constitutively de-repressed. Is it expressed as protein, and is it a physiologically active GEF?
Suggested experts: Katoh laboratory, Park laboratory, UniProt
Experiment: Side-by-side in vitro exchange kinetics of the purified ARHGEF16 DH-PH cassette against a panel of Rho-family GTPases - RhoG, Rac1, Rac2, Rac3, Cdc42, RhoA, RhoB, RhoC, RhoQ, RhoJ - with the equivalent cassette from Ephexin-1 as the promiscuous comparator and a catalytically dead DH mutant as the negative. Mant-GDP release rates give a quantitative specificity profile rather than a binary answer, and would establish whether the cell-based negatives reflect true catalytic selectivity or a failure of the autoinhibited full-length protein to open.
Hypothesis: Ephexin-4 is a strictly RhoG-specific exchange factor, and the specificity resides in the DH-PH cassette rather than in the regulatory regions.
Type: biochemical
Experiment: Introduce E291A into human ARHGEF16 - the published mutant is murine, and human position 295 is a serine - and compare wild type, E291A, and the PDZ-motif deletion for RhoG-GTP levels, oligomer formation by chemical cross-linking, and rate of exchange on purified protein. Including the substrate panel above on the de-repressed protein tests whether relieving autoinhibition also broadens specificity, which is the alternative explanation for the Cdc42 result obtained with Tip-1 and E6 present.
Hypothesis: The E291A substitution (human numbering; murine E295A) de-represses ARHGEF16 by disrupting the intermolecular autoinhibition interface, and the de-repressed protein is more active without being differently specific.
Type: biochemical
Experiment: Repeat the CRIB pull-down for Cdc42-GTP in cells expressing ARHGEF16 alone, ARHGEF16 plus TAX1BP3, ARHGEF16 plus HPV16 E6, and all three, in the same cell background and with Zizimin1 as the positive control used in the original negative experiment. A conditional result would let the GO:0032489 annotations be qualified rather than left contradicting the RhoG paper.
Hypothesis: The Cdc42 activity reported in PMID:21139582 is conditional on TAX1BP3 and HPV16 E6 rather than intrinsic, which would reconcile it with the Cdc42 negatives in PMID:20679435.
Type: cell biology
Experiment: Confirm endogenous protein expression of isoform 2 by isoform-resolved mass spectrometry or an N-terminus-specific antibody, then compare isoform 1 and isoform 2 for basal RhoG-GTP, responsiveness to ELMO1 and to PDZ-protein co-expression, and oligomerisation. A constitutively active isoform would make the autoinhibition mechanism a splice-controlled switch rather than only a partner-controlled one.
Hypothesis: Isoform 2 (Q5VV41-2), which begins after the autoinhibitory region, is a constitutively active RhoG exchange factor.
Type: cell biology
Experiment: In Ephexin4-knockdown cells, test whether constitutively active RhoG targeted to the plasma membrane rescues chromosome alignment while a cytoplasmically restricted active RhoG does not, and whether the rescue survives in cells whose cortical actomyosin is separately perturbed. This distinguishes a cortical-rigidity mechanism from a direct mitotic one and would determine which GO process term, if any, is appropriate.
Hypothesis: ARHGEF16 contributes to metaphase chromosome alignment through cortical RhoG rather than through any spindle-associated activity.
Type: cell biology
What is not known — curated, literature-grounded statements of the open unknowns (the inverse of core functions).
Gap: GO has no term in which to state that this protein's exchange substrate is RhoG and only RhoG. Every substrate-specific handle has been merged into a general parent: GO:0005089 Rho guanyl-nucleotide exchange factor activity, GO:0030676 Rac and GO:0005088 Ras into GO:0005085; GO:0017048 Rho GTPase binding into GO:0031267; GO:0032860 and GO:0032861 activation of Rho and Rac GTPase activity into GO:0090630. None of the four general parents has an is_a child.
OPEN ONTOLOGY MF_DARK
What is known: The biology is not in doubt. Exchange on RhoG was measured on purified DH-PH protein, and the negatives for Rac1, Cdc42 and RhoA were measured in the same paper with Dock180, Zizimin1 and Ephexin1 as positive controls. What is missing is a place to put it: the fact separates ARHGEF16 from four RhoA-GEF siblings that share its GO molecular function verbatim.
Significance: A family-level IBA at GO:0005085 is unfalsifiable for substrate: it transfers the same term from three RhoA GEFs to the one family member that does not act on RhoA, and nothing in the record registers the difference. The structural analysis shows the sequence cannot fill the gap either. Holding the GEF constant and changing the bound GTPase barely changes the surface - the Dbs contact sets from the Cdc42-bound and RhoA-bound structures share a Jaccard of 0.73 and move ARHGEF16's score by 0.06 - so the panel ranks by GEF-to-GEF similarity rather than by substrate, and would name Cdc42 for a protein whose measured substrate is RhoG.
What would resolve it: No new term is proposed; GO merged these deliberately, and re-proposing them would argue with a decision rather than record a gap. The available mechanism is the annotation extension: has_input on the GO:0005085 and GO:0090630 rows, which this review supplies. If GO wants substrate recoverable without extensions, the decision to revisit is the merge itself.
Provenance (the field's own admissions):
Gap: Almost nothing in this protein's literature has reached GO. Of the 26 PubMed records naming Ephexin4 or ARHGEF16, exactly two produced a GO annotation on the human or mouse protein. The autoinhibition mechanism, the anoikis role, the EphA2-Ser897 input, the efferocytosis work and the mitotic phenotype are all uncurated.
OPEN CURATION BP_DARK
What is known: This is a curation gap, not an evidence gap. The uncurated papers include three structural or biochemical studies of the autoinhibition mechanism, two anoikis papers with knockdown and rescue in human cells, and a 2025 study with knockdown, rescue and a phospho-mimic allele. Mouse Arhgef16 has no experimental GO annotation of any kind: its entire record is projected from human by ISO and Ensembl Compara, which means the mouse efferocytosis work has nowhere to land either.
Significance: The gene reads as sparsely characterised when it is not. It also makes the record fragile: with only two curated papers, the single mis-typed molecular function from one of them has been projected to 83 annotations across 81 taxa.
What would resolve it: Curation of PMID:21621533, PMID:23772378, PMID:28667327, PMID:30445756, PMID:33597305 and PMID:39675713 on human ARHGEF16, and of PMID:25063526 on mouse Arhgef16. This review proposes only the anoikis term as NEW; the others need decisions about term choice that are better made by a curator with the full datasets.
Provenance (the field's own admissions):
Gap: Where in the cell ARHGEF16 sits has never been measured. Both cellular-component terms on the gene are inferences - cytoplasm from a UniProt keyword mapping and cytosol from an ARBA rule and two Reactome reactions - and UniProt's own SUBCELLULAR LOCATION line carries ECO:0000305, an author-inferred code, not an experimental one.
OPEN BIOLOGYCURATION CC_DARK
What is known: The functional geography is partly known even though the localisation is not: the protein acts on RhoG at the plasma membrane, its knockdown reduces RhoG localization there, and its activity assembles a complex with EPHA2 at the tips of cortactin-rich protrusions. What is missing is a direct observation of where ARHGEF16 itself is, and whether it is recruited to the membrane or acts on RhoG from a cytoplasmic pool.
Significance: The two autoinhibitory modes are relieved by membrane-proximal events - ELMO binding and PDZ-scaffold binding - so whether the protein is recruited before or after de-repression is the difference between two mechanistic models of how this GEF is switched on.
What would resolve it: Endogenous-tagging plus imaging, with and without EPHA2 Ser897 phosphorylation, would settle it; a curated IDA for the localisation would follow.
Provenance (the field's own admissions):
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