AFAP1L2 (XB130, PI3KAP) is an 818-residue intracellular adaptor and actin-associated scaffold of the AFAP family. Its N-terminal region carries proline-rich SH3-binding and tyrosine-containing SH2-binding motifs, followed by two pleckstrin homology domains and a C-terminal coiled-coil and actin-binding region. It is a substrate of Src-family and RET/PTC tyrosine kinases. Once tyrosine phosphorylated, Tyr54 docks the SH2 domains of the PI3K regulatory subunit p85alpha, coupling these kinases to PI3K-Akt signaling that sustains G1/S progression and cell survival. It also binds Src and enhances Src activation. Its N-terminus binds the fifth SH3 domain of the scaffold Tks5. XB130 is cytoplasmic at rest and translocates to the branched F-actin of lamellipodia on Rac activation or EGF stimulation. The rodent ortholog binds and crosslinks actin filaments by multimerizing. In thyroid follicular cells, where expression is highest, the mouse protein sits at the apical membrane and is needed for apical membrane organization, follicle lumen formation and thyroid hormone production.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005737 cytoplasm | IDA PMID:17412687 XB130, a novel adaptor protein for signal transduction. | ACCEPT | Summary: XB130 is a cytoplasmic adaptor at rest; this is the basal location from which it is recruited to lamellipodial F-actin and, in thyrocytes, to the apical cortex. Reason: The original characterization and the curated UniProt location place XB130 in the cytoplasm. Lodyga et al. 2010 describe it as a cytosolic adaptor that translocates to the cell periphery on stimulation. The Tks5 study shows endogenous XB130 in cytoplasmic and perinuclear puncta. Cytoplasm is correct and appropriately broad for the resting protein. The more specific dynamic locations (lamellipodium, apical plasma membrane) are proposed as NEW rows. Supporting Evidence: file:human/AFAP1L2/AFAP1L2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17412687}. PMID:21084565 XB130 is a newly described cytosolic adaptor protein and tyrosine kinase substrate PMID:26446840 Coimmunofluorescence microscopy showed that endogenous XB130 and Tks5 are colocalized in fine punctate structures in the cytoplasm and in perinuclear regions |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic mapping of the curated UniProt location Cytoplasm, which rests on PMID:17412687. Reason: The SubCell mapping reproduces a curated, publication-backed location. It agrees with the IDA row for the same term. Supporting Evidence: file:human/AFAP1L2/AFAP1L2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17412687}. PMID:21084565 XB130 is a newly described cytosolic adaptor protein and tyrosine kinase substrate PMID:26446840 Coimmunofluorescence microscopy showed that endogenous XB130 and Tks5 are colocalized in fine punctate structures in the cytoplasm and in perinuclear regions |
| GO:0005829 cytosol | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT places cytosol at the deuterostome-level AFAP family node PTN001023816. Human XB130 is the seed. Reason: Every characterized AFAP family member (AFAP1, AFAP1L1, AFAP1L2) is a soluble, non-membrane-spanning adaptor that is recruited to actin structures from a cytosolic pool. XB130 has no transmembrane segment or signal peptide in UniProt. Human XB130 sits inside the clade that inherits the node, and there is no evidence of a lineage-specific loss. Its own cytoplasmic/cytosolic IDA data are the expected descendant evidence and are not circular. Supporting Evidence: file:human/AFAP1L2/AFAP1L2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17412687}. PMID:21084565 XB130 is a newly described cytosolic adaptor protein and tyrosine kinase substrate PMID:26446840 Coimmunofluorescence microscopy showed that endogenous XB130 and Tks5 are colocalized in fine punctate structures in the cytoplasm and in perinuclear regions |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Human Protein Atlas immunofluorescence curation places AFAP1L2 in the cytosol. This is consistent with the published cytoplasmic distribution. Reason: The HPA immunofluorescence curation agrees with the published cytoplasmic distribution of XB130 and with the IBA row for the same term. Supporting Evidence: file:human/AFAP1L2/AFAP1L2-uniprot.txt CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17412687}. PMID:21084565 XB130 is a newly described cytosolic adaptor protein and tyrosine kinase substrate PMID:26446840 Coimmunofluorescence microscopy showed that endogenous XB130 and Tks5 are colocalized in fine punctate structures in the cytoplasm and in perinuclear regions |
| GO:0006954 inflammatory response | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: The only basis is reduced IL-8 (and IL-6) release from a human bronchial epithelial cell line after XB130 siRNA. PAINT propagated it from the human IDA to the AFAP1L2 subfamily node PTN002682769. Reason: Reduced cytokine output from cultured BEAS-2B cells shows that XB130 signaling affects IL-8 and IL-6 production in that cell type. It does not show that XB130 does any of the work of an organismal inflammatory response. No in vivo inflammation model with XB130 loss is cited for this row. The cytokine effect is already captured, at the right specificity, by the existing IL-8 and IL-6 production rows. I do not dispute the node placement, since human is the only seed and the subfamily is a clean 1:1 AFAP1L2 ortholog group. What I mark is the scope of the term, which says more than the descendant evidence. The row is kept but not core. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002682769 SOURCE WEAK OR INFERRED AFAP1L2-subfamily node (Euteleostomi), seeded only by the human IDA from PMID:17412687. That IDA rests on IL-8 and IL-6 release from a cultured epithelial line, so it supports the cytokine-production terms rather than an organismal inflammatory response. Supporting Evidence: PMID:17412687 Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3beta, and altered cell cycles in human lung epithelial cells. file:human/AFAP1L2/AFAP1L2-Xu2007-excerpt.md In addition to IL-8, the protein level of IL-6 was also reduced by siRNA treatment. |
| GO:0006954 inflammatory response | IDA PMID:17412687 XB130, a novel adaptor protein for signal transduction. | MARK AS OVER ANNOTATED | Summary: Cell-line cytokine readout (IL-8, IL-6 after XB130 siRNA) annotated to the organismal inflammatory response. Reason: The experiment measures cytokine release from cultured airway epithelial cells. It supports regulation of IL-8 and IL-6 production, which other rows capture, but not participation in an inflammatory response. The action matches the IBA row for this term. Supporting Evidence: PMID:17412687 Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3beta, and altered cell cycles in human lung epithelial cells. file:human/AFAP1L2/AFAP1L2-Xu2007-excerpt.md In addition to IL-8, the protein level of IL-6 was also reduced by siRNA treatment. |
| GO:0007346 regulation of mitotic cell cycle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: XB130 knockdown impairs G1/S progression in airway epithelial and thyroid carcinoma cells. This follows from its role as a PI3K-Akt adaptor. Reason: Three independent studies report altered cell-cycle distribution after XB130 depletion. In Xu 2007 it is altered cell cycles; in Lodyga 2009 it is inhibited cell-cycle progression in TPC1 cells; in Moodley 2015 it is G1 accumulation with p21 up-regulation in BEAS-2B cells. Lodyga 2009 links this to loss of PI3K-Akt coupling. XB130 regulates the cell cycle as an upstream signaling adaptor, not as a component of the cell-cycle machinery, so the term is kept but marked non-core. Supporting Evidence: PMID:17412687 Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3beta, and altered cell cycles in human lung epithelial cells. PMID:19060924 downregulation of XB130 in TPC1 papillary thyroid cancer cells, harboring the RET/PTC1 kinase, strongly reduced Akt activity without altering ERK1/2 phosphorylation, and concomitantly inhibited cell-cycle progression and survival in suspension PMID:26446840 Down-regulation of XB130 and/or Tks5 results in the accumulation of cells in the G1 (resting) phase and a decrease of cells in the DNA synthesis and G2 cell growth phase |
| GO:0007346 regulation of mitotic cell cycle | IDA PMID:17412687 XB130, a novel adaptor protein for signal transduction. | KEEP AS NON CORE | Summary: siRNA depletion of XB130 altered cell-cycle distribution in human lung epithelial cells. Reason: This is the same downstream signaling consequence as the IBA row. It is supported and replicated in later studies, but it is not core. Supporting Evidence: PMID:17412687 Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3beta, and altered cell cycles in human lung epithelial cells. PMID:19060924 downregulation of XB130 in TPC1 papillary thyroid cancer cells, harboring the RET/PTC1 kinase, strongly reduced Akt activity without altering ERK1/2 phosphorylation, and concomitantly inhibited cell-cycle progression and survival in suspension PMID:26446840 Down-regulation of XB130 and/or Tks5 results in the accumulation of cells in the G1 (resting) phase and a decrease of cells in the DNA synthesis and G2 cell growth phase |
| GO:0017124 SH3 domain binding | IPI PMID:17412687 XB130, a novel adaptor protein for signal transduction. | ACCEPT | Summary: XB130's N-terminal proline-rich SH3-binding motif engages SH3 domains. These include c-Src (this IPI) and the fifth SH3 domain of Tks5. Reason: Xu 2007 shows the XB130-Src interaction. Deleting the N-terminal region that holds the SH3-binding motif impairs Src signaling. Moodley 2015 maps the binding directly. XB130 binds only the fifth SH3 domain of Tks5, and both the Tks5 W1108A mutation in that SH3 ligand pocket and XB130 P101A in the PPPxxxP motif reduce binding. SH3 domain binding is the specific adaptor activity of the motif-rich N-terminus. AFAP1L2 has no SH3 domain itself. Supporting Evidence: PMID:17412687 XB130DeltaN, an N-terminal deletion mutant lacking a putative SH3-binding motif and several putative SH2-binding sites, reduced its ability to mediate Src signal transduction. PMID:26446840 XB130 was found to bind specifically to the fifth SH3 domain of Tks5 |
| GO:0030296 protein tyrosine kinase activator activity | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT places Src-activator activity at the AFAP1L2 subfamily node PTN002682769 (Euteleostomi), seeded by human XB130. Reason: Co-expression of XB130 with c-Src raises Src activity and tyrosine phosphorylation of cellular proteins. Endogenous XB130 depletion lowers c-Src activity (Xu 2007) and blocks FBS- or EGF-induced Src Y416 phosphorylation (Moodley 2015). In rat thyroid cells, Src associates with PI3KAP/XB130 and is activated in a Src-dependent cAMP response (Yamanaka 2012). The node sits in the AFAP1L2-specific subfamily (PTHR14338:SF4) and is not propagated to AFAP1 or AFAP1L1, which keeps the inference within the 1:1 ortholog clade. The term says XB130 activates a kinase without being one, which is accurate. Supporting Evidence: PMID:17412687 Their co-expression in COS-7 cells resulted in activation of c-Src and elevated tyrosine phosphorylation of multiple proteins, including XB130 itself. PMID:17412687 Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3beta, and altered cell cycles in human lung epithelial cells. PMID:26446840 Down-regulation of XB130, Tks5, or both XB130 and Tks5 inhibited the FBS- or EGF-induced tyrosine phosphorylation of cellular proteins and inhibited the phosphorylation of Src Y416 |
| GO:0030296 protein tyrosine kinase activator activity | IDA PMID:17412687 XB130, a novel adaptor protein for signal transduction. | ACCEPT | Summary: Co-expression of XB130 activates c-Src, and depletion reduces endogenous c-Src activity. Reason: This is the primary evidence for the Src-activating adaptor function. It is consistent with the IBA row and with the later Tks5 study. Supporting Evidence: PMID:17412687 Their co-expression in COS-7 cells resulted in activation of c-Src and elevated tyrosine phosphorylation of multiple proteins, including XB130 itself. PMID:17412687 Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3beta, and altered cell cycles in human lung epithelial cells. PMID:26446840 Down-regulation of XB130, Tks5, or both XB130 and Tks5 inhibited the FBS- or EGF-induced tyrosine phosphorylation of cellular proteins and inhibited the phosphorylation of Src Y416 |
| GO:0032675 regulation of interleukin-6 production | IDA PMID:17412687 XB130, a novel adaptor protein for signal transduction. | KEEP AS NON CORE | Summary: XB130 siRNA reduced IL-6 protein release from BEAS-2B airway epithelial cells. The result is reported in the full-text Results. Reason: The result is a single cell-line readout of a downstream signaling output. It supports the regulation term in that context, but it is not a core function. The PMID cache is abstract-only, so the IL-6 sentence is preserved in a separate excerpt file inspected from the full paper. The curator saw the full text. Supporting Evidence: file:human/AFAP1L2/AFAP1L2-Xu2007-excerpt.md In addition to IL-8, the protein level of IL-6 was also reduced by siRNA treatment. |
| GO:0032757 positive regulation of interleukin-8 production | IDA PMID:17412687 XB130, a novel adaptor protein for signal transduction. | KEEP AS NON CORE | Summary: XB130 depletion reduced IL-8 production in human lung epithelial cells. Reason: Loss of XB130 lowered IL-8 output, so the sign of the regulation term is correct. It is a downstream consequence of Src signaling in one epithelial context and is not core. Supporting Evidence: PMID:17412687 Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3beta, and altered cell cycles in human lung epithelial cells. |
| GO:0042169 SH2 domain binding | IPI PMID:17412687 XB130, a novel adaptor protein for signal transduction. | ACCEPT | Summary: Tyrosine-phosphorylated XB130 motifs are docking sites for SH2 domains, including Src (this IPI) and the p85alpha subunit of PI3K (pTyr54). Reason: Xu 2007 shows that the N-terminal region with putative SH2-binding sites is needed for Src signaling. Lodyga 2009 identifies Tyr54 as the main RET/PTC phosphorylation site and as a critical binding site for the p85alpha SH2 domains. This SH2-docking function is the mechanistic core of the adaptor. The more specific p85-binding activity is proposed as a NEW row. Supporting Evidence: PMID:17412687 XB130DeltaN, an N-terminal deletion mutant lacking a putative SH3-binding motif and several putative SH2-binding sites, reduced its ability to mediate Src signal transduction. PMID:19060924 We identified tyrosine 54 of XB130 as the major target of RET/PTC-mediated phosphorylation and a critical binding site for the SH2 domains of p85alpha. |
| GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: XB130 is needed for full EGF-induced Akt and GSK3beta phosphorylation and EGF-induced Src activation in airway epithelial cells. Reason: The EGF evidence (Xu 2007; Moodley 2015) supports positive regulation of downstream EGF receptor signaling, probably through the same Src and p85-PI3K docking mechanism. XB130 also couples RET/PTC, TSH/cAMP-Src and serum signaling to PI3K. EGFR is therefore one input among several rather than the defining pathway. The PI3K-Akt coupling is the core process and is proposed as NEW. This row is kept, but as non-core. Supporting Evidence: PMID:17412687 Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3beta, and altered cell cycles in human lung epithelial cells. PMID:26446840 XB130 and/or Tks5 siRNA also blocked FBS- or EGF-induced phosphorylation of PI3K p85Ξ± subunit and Akt |
| GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway | IDA PMID:17412687 XB130, a novel adaptor protein for signal transduction. | KEEP AS NON CORE | Summary: XB130 depletion reduces EGF-induced Akt and GSK3beta phosphorylation. Reason: The action matches the IBA row. This is a supported, context-specific signaling role. Supporting Evidence: PMID:17412687 Down-regulation of endogenous XB130 with siRNA reduced c-Src activity, IL-8 production, EGF-induced phosphorylation of Akt and GSK3beta, and altered cell cycles in human lung epithelial cells. PMID:26446840 XB130 and/or Tks5 siRNA also blocked FBS- or EGF-induced phosphorylation of PI3K p85Ξ± subunit and Akt |
| GO:0045893 positive regulation of DNA-templated transcription | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: The only basis is SRE- and AP-1-luciferase reporter enhancement when XB130 is overexpressed with c-Src in HEK293 cells. Reason: XB130 is a cytoplasmic adaptor with no DNA-binding domain or nuclear role. The reporter gain is a distal readout of its Src-activating activity, many signaling steps upstream of the transcription factors. GO convention does not use transcription-regulation process terms for upstream cytoplasmic signaling components without a more direct link. The Src-activator MF and the PI3K-Akt signaling process describe the real contribution. The PAINT curator propagated what the human IDA asserted. The node placement is not at fault; the scope of the term is. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002682769 SOURCE WEAK OR INFERRED Node seeded only by the human IDA from PMID:17412687, which is an SRE/AP-1 luciferase reporter gain with overexpressed XB130 and c-Src. That treats an upstream cytoplasmic adaptor as a transcription regulator. Supporting Evidence: PMID:17412687 XB130 expression in HEK293 cells enhanced serum response element- and AP-1-dependent transcriptional activation mediated by c-Src. |
| GO:0045893 positive regulation of DNA-templated transcription | IDA PMID:17412687 XB130, a novel adaptor protein for signal transduction. | MARK AS OVER ANNOTATED | Summary: Reporter-gene enhancement downstream of Src by an overexpressed cytoplasmic adaptor. Reason: The action matches the IBA row. The experiment supports Src signaling output, not regulation of transcription by AFAP1L2 itself. Supporting Evidence: PMID:17412687 XB130 expression in HEK293 cells enhanced serum response element- and AP-1-dependent transcriptional activation mediated by c-Src. |
| GO:0036312 phosphatidylinositol 3-kinase regulatory subunit binding | IPI PMID:19060924 XB130, a tissue-specific adaptor protein that couples the RE... | NEW | Summary: Tyrosine-phosphorylated XB130 (pTyr54, YxxM) binds the SH2 domains of the PI3K regulatory subunit p85alpha. Reason: This is the defining adaptor contact by which XB130 links RET/PTC and Src to PI3K. Lodyga 2009 mapped it to Tyr54 in human XB130. The rat ortholog PI3KAP/XB130 (PTHR14338:SF4) was independently identified as the p125 protein that associates with p85 PI3K and carries PI3K activity (Yamanaka 2012). It is informative where SH2 domain binding alone is not, because it names the partner class and the pathway it couples to. Supporting Evidence: PMID:19060924 We identified tyrosine 54 of XB130 as the major target of RET/PTC-mediated phosphorylation and a critical binding site for the SH2 domains of p85alpha. PMID:22496359 cAMP treatment elevated PI3KAP/XB130 mRNA and protein levels as well as tyrosine phosphorylation and interaction with p85 PI3K leading to increased PI3K activities associated with PI3KAP/XB130 |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IMP PMID:19060924 XB130, a tissue-specific adaptor protein that couples the RE... | NEW | Summary: XB130 couples RET/PTC (and Src) tyrosine kinase activity to PI3K-Akt signaling. Its depletion strongly reduces Akt activity without affecting ERK. Reason: Participation test: XB130 is not just required for the pathway. It contributes the phosphotyrosine docking site (Tyr54) that recruits p85alpha, a scaffold contribution to the signaling step itself. Depletion lowers Akt activity selectively in TPC1 cells (Lodyga 2009) and lowers EGF/FBS-induced p85alpha and Akt phosphorylation in BEAS-2B cells (Moodley 2015). Comparator check: other docking adaptors that recruit p85 through YxxM motifs, carry the term: QuickGO, checked 2026-10-20, lists GO:0051897 for human IRS1 (P35568, ISS) and GAB1 (Q13480, TAS). So the term is used for this adaptor role and is not reserved for the kinases. Supporting Evidence: PMID:19060924 downregulation of XB130 in TPC1 papillary thyroid cancer cells, harboring the RET/PTC1 kinase, strongly reduced Akt activity without altering ERK1/2 phosphorylation, and concomitantly inhibited cell-cycle progression and survival in suspension PMID:19060924 We identified tyrosine 54 of XB130 as the major target of RET/PTC-mediated phosphorylation and a critical binding site for the SH2 domains of p85alpha. PMID:26446840 XB130 and/or Tks5 siRNA also blocked FBS- or EGF-induced phosphorylation of PI3K p85Ξ± subunit and Akt |
| GO:0051015 actin filament binding | ISS PMID:27462298 Phosphatidylinositol 3-Kinase-Associated Protein (PI3KAP)/XB... | NEW | Summary: The C-terminal actin-binding region of PI3KAP/XB130 binds F-actin directly in vitro and is conserved across vertebrate orthologs, including human. Reason: Yamanaka 2016 used mouse PI3KAP/XB130 (variant 1). Its ortholog Q5DTU0 sits in the same PANTHER subfamily PTHR14338:SF4 as human Q8N4X5. A GST fusion of the C-terminal region co-sedimented with F-actin, and the full-length recombinant protein crosslinked filaments. The authors' alignment shows the binding region is highly conserved in vertebrate XB130 orthologs, human included. Lodyga 2010 shows independently that human XB130 associates with lamellipodial branched F-actin through its N- and C-terminal regions. The transfer rests on subfamily membership and conservation of the mapped region, not on name or best hit. This region differs from the classical actin-binding domain of AFAP1 and AFAP1L1, so the function is not inferred from those paralogs. Supporting Evidence: PMID:27462298 that the carboxyl terminal region of PI3KAP/XB130 containing amino acid residues 830-840 was required and sufficient for localization to F-actin in NIH3T3 cells, and this region is directly bound to F-actin in vitro PMID:27462298 Furthermore, homology search analysis revealed that this region was highly conserved in many vertebrate species (Figure 2C). PMID:27462298 However, this motif is not conserved in mouse PI3KAP/XB130 that we used in this study (variant 1; GenBank Accession |
| GO:0030027 lamellipodium | IDA PMID:21084565 Adaptor protein XB130 is a Rac-controlled component of lamel... | NEW | Summary: On EGF, wounding or active Rac, XB130 translocates to the cell periphery and localizes to the lamellipodial F-actin meshwork. Reason: Lodyga 2010 is a dedicated localization and structure-function study of XB130 in lamellipodia. Recruitment depends on branched F-actin and on the XB130 N- and C-termini. Endogenous XB130 silencing in human TPC1 cells reduced lamellipodial persistence. This stimulus-dependent location adds information beyond cytoplasm. Only the abstract is cached; the localization claim is stated in it. Supporting Evidence: PMID:21084565 In stimulated cells, XB130 localized to the lamellipodial F-actin meshwork. |
| GO:0016324 apical plasma membrane | ISS PMID:34470464 XB130 Deficiency Causes Congenital Hypothyroidism in Mice du... | NEW | Summary: In thyroid follicular cells, endogenous XB130 is mainly at the apical membrane, at both embryonic and postnatal stages (mouse). Reason: Wang et al. 2021 localized endogenous mouse XB130 (Q5DTU0, same PANTHER subfamily PTHR14338:SF4 as human) to the apical membrane of thyrocytes. In its absence, apical microvilli, ezrin and TPO staining and follicle lumen formation are disrupted. Thyroid is also where human AFAP1L2 expression is highest. The location is a structural fact about the 1:1 ortholog in its main tissue. The knockout phenotypes (congenital hypothyroidism, delayed folliculogenesis) are not proposed as process annotations, because they are necessity evidence and the mechanism linking the scaffold to each step is not resolved. Supporting Evidence: PMID:34470464 XB130 was found mainly on the apical membrane of thyroid follicles. |
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Download this section (compressed HTML)Q: Does the C-terminal actin-binding region mapped in mouse PI3KAP/XB130 (residues 830-840 of the mouse construct) correspond to a conserved segment near the C-terminus of the 818-residue human protein, and does human XB130 crosslink F-actin in vitro?
Q: Which PH domain lipid specificities, if any, target XB130 to the thyrocyte apical membrane, and is the thyroid apical-cortex role conserved in human (are AFAP1L2 variants found in congenital hypothyroidism cohorts)?
Experiment: Purify recombinant human XB130 (full length, and with C-terminal and N-terminal-40 deletions). Test F-actin co-sedimentation and low-speed crosslinking assays, and test multimerization by blue-native PAGE, so the actin-binding function is established directly on the human protein.
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