FERMT2 encodes kindlin-2, a broadly expressed FERM/PH domain-containing adaptor that localizes to focal adhesions, the cytoplasmic side of membranes, cytoskeleton, cell cortex, and related adhesion structures. Kindlin-2 binds integrin cytoplasmic tails and phosphoinositide-rich membranes, cooperates with talin to promote integrin activation, and links cell-extracellular matrix adhesions to focal adhesion assembly, actin organization, cell spreading, and cell-shape control. It also participates in context-specific signaling branches including Wnt/beta-catenin, TGF-beta/Smad, adherens-junction vascular barrier regulation, and mesenchymal stem-cell fate control.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0007160 cell-matrix adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: Enhances integrin-mediated cell adhesion onto the extracellular matrix, requiring both integrin and phospholipid binding; the precise adhesion process at kindlin-2's core. Reason: Cell-matrix adhesion is the defining biological process of kindlin-2. |
| GO:0005178 integrin binding | IBA GO_REF:0000033 | ACCEPT | Summary: Direct binding of the membrane-distal NPxY region of integrin beta (ITGB1/ITGB3) cytoplasmic tails is kindlin-2's signature molecular activity and the basis of co-activation with talin. Reason: Integrin-tail binding is the defining molecular function of kindlin-2. |
| GO:0005925 focal adhesion | IBA GO_REF:0000033 | ACCEPT | Summary: Focal adhesion is the defining subcellular site of kindlin-2, where it co-localizes with actin stress fibers at cell-ECM adhesions and recruits partners such as FBLIM1. Reason: Focal adhesion is the central, defining localization of kindlin-2. |
| GO:0001725 stress fiber | IEA GO_REF:0000120 | ACCEPT | Summary: Co-localizes with actin stress fibers at cell-ECM focal adhesion sites, reflecting the physical link kindlin-2 establishes between integrin adhesions and the contractile cytoskeleton. Reason: Stress-fiber association reflects the core integrin-to-actin linkage. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Nuclear localization underlies kindlin-2's moonlighting role in Wnt/beta-catenin transcriptional regulation; distinct from its principal cytoplasmic focal-adhesion function. Reason: Secondary nuclear/transcriptional role, separate from the core integrin-adhesion function. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Kindlin-2 is a cytoplasmic protein (IDA); consistent with its role as a cytosolic adapter recruited to membrane-proximal integrin tails and focal adhesions. Reason: Bulk cytoplasmic localization matches a cytoplasmic adhesion adapter. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoskeletal localization reflects kindlin-2 association with the actin network at adhesion sites, consistent with its integrin-to-cytoskeleton linker function. Reason: Cytoskeletal association supports the core integrin-actin linkage role. |
| GO:0005925 focal adhesion | IEA GO_REF:0000044 | ACCEPT | Summary: Focal adhesion is the defining subcellular site of kindlin-2, where it co-localizes with actin stress fibers at cell-ECM adhesions and recruits partners such as FBLIM1. Reason: Focal adhesion is the central, defining localization of kindlin-2. |
| GO:0005938 cell cortex | IEA GO_REF:0000044 | ACCEPT | Summary: Cytoplasmic, cell-cortex localization (peripheral membrane, cytoplasmic side) is where kindlin-2 engages integrin tails and the submembranous actin network at adhesion sites. Reason: Cortical/submembranous localization is intrinsic to its membrane-proximal integrin-adapter action. |
| GO:0007229 integrin-mediated signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: Initiates/propagates integrin-mediated (inside-out and outside-in) signaling through integrin-tail engagement and adhesome assembly; a core signaling process for kindlin-2. Reason: Integrin signaling is a core pathway directly engaged by kindlin-2. |
| GO:0009986 cell surface | IEA GO_REF:0000044 | MODIFY | Summary: Kindlin-2 is a cytoplasmic peripheral-membrane protein acting on the inner leaflet; 'cell surface' (extracellular face, IEA) misplaces it. The accurate site is the cytoplasmic side of the plasma membrane. Reason: IEA 'cell surface' implies extracellular face; kindlin-2 is cytoplasmic, on the inner membrane leaflet. Proposed replacements: cytoplasmic side of plasma membrane |
| GO:0016020 membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Peripheral membrane association (cytoplasmic side) via PH-domain phosphoinositide and N-terminal lipid binding underlies kindlin-2's membrane-proximal integrin engagement. Reason: Membrane association via lipid binding is integral to membrane-proximal integrin activation. |
| GO:0030335 positive regulation of cell migration | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: Promotes cell migration (IMP), a downstream behavior enabled by kindlin-2-driven focal-adhesion dynamics and integrin activation rather than a defining molecular function. Reason: Migration is a downstream cellular behavior of the integrin-adhesion core. |
| GO:0031258 lamellipodium membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Kindlin-2 co-localizes with ITGB3 at lamellipodia at the leading edge of spreading cells, a membrane site directly tied to integrin activation during spreading. Reason: Leading-edge membrane localization is part of its integrin-activation/spreading role. |
| GO:0031674 I band | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Sarcomeric I-band localization (ISS to mouse) reflects kindlin-2 at the myotendinous/costameric integrin adhesions of striated muscle, a tissue-specific context of its adhesion role rather than its defining site. Reason: Muscle-specific localization downstream of the core integrin-adhesion adapter function; not the primary site of action. |
| GO:0005515 protein binding | IPI PMID:22699938 Kindlin 2 forms a transcriptional complex with Ξ²-catenin and... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (IPI) is uninformative for an adapter with many defined partners (integrins, FBLIM1, ILK, CTNNB1); specific binding terms already capture the meaningful interactions. Reason: Generic uninformative MF; specific partner-binding terms are preferable. |
| GO:0007160 cell-matrix adhesion | IEA GO_REF:0000107 | ACCEPT | Summary: Enhances integrin-mediated cell adhesion onto the extracellular matrix, requiring both integrin and phospholipid binding; the precise adhesion process at kindlin-2's core. Reason: Cell-matrix adhesion is the defining biological process of kindlin-2. |
| GO:0033622 integrin activation | IEA GO_REF:0000107 | ACCEPT | Summary: Co-activates integrins with talin: binding the membrane-distal beta-tail NPxY motif, kindlin-2 enhances affinity maturation; QW614-615AA abolishes ITGB3 binding and activation enhancement. Reason: Integrin (co-)activation is the central molecular process defining kindlin-2. |
| GO:0034334 adherens junction maintenance | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Kindlin-2 contributes to maintaining adherens junctions, a downstream tissue-integrity role distinct from its proximal integrin/focal-adhesion adapter activity. Reason: Downstream junction-maintenance process, not the proximal integrin-adhesion function. |
| GO:0034446 substrate adhesion-dependent cell spreading | IEA GO_REF:0000107 | ACCEPT | Summary: Mediates substrate adhesion-dependent cell spreading (ISS); kindlin-2 enhancement of ECM adhesion and lamellipodial integrin engagement drives cell spreading. Reason: Substrate-dependent spreading is a core process driven by kindlin-2 adhesion activity. |
| GO:0043116 negative regulation of vascular permeability | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Reduces vascular permeability (IMP) via endothelial adhesion/junction integrity, a physiological consequence of kindlin-2 adhesion function rather than its proximal molecular role. Reason: Endothelial-barrier phenotype downstream of the core adhesion role. |
| GO:0045599 negative regulation of fat cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Inhibits adipocyte differentiation (IMP), a cell-fate output of kindlin-2 adhesion/signaling crosstalk, downstream and tissue-specific relative to the integrin-adapter core. Reason: Cell-differentiation output downstream of adhesion signaling, not the core function. |
| GO:0045669 positive regulation of osteoblast differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Promotes osteoblast differentiation (IMP), a skeletal cell-fate output linked to integrin/fibronectin adhesion; downstream and tissue-specific relative to the adapter core. Reason: Tissue-specific differentiation output downstream of integrin adhesion. |
| GO:0048041 focal adhesion assembly | IEA GO_REF:0000107 | ACCEPT | Summary: Kindlin-2 is required for focal-adhesion assembly; its integrin co-activation nucleates the adhesion complex, a core process supported by IMP/ISS evidence. Reason: Focal-adhesion assembly is a core process requiring kindlin-2. |
| GO:0051015 actin filament binding | IEA GO_REF:0000107 | ACCEPT | Summary: Binding actin filaments anchors integrin adhesion complexes to the contractile cytoskeleton, supporting kindlin-2's role linking focal adhesions to stress fibers. Reason: Specific cytoskeletal-binding activity supporting the core integrin-actin linker role. |
| GO:0060173 limb development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Limb development (IEA) is an organismal phenotype downstream of kindlin-2-dependent integrin adhesion in developing tissues; a developmental consequence, not the molecular core. Reason: Organ-development phenotype downstream of the integrin-adhesion adapter role. |
| GO:0072657 protein localization to membrane | IEA GO_REF:0000107 | ACCEPT | Summary: Recruits/retains partners at the plasma membrane (ISS) as part of assembling the membrane-proximal integrin adhesion complex; integral to kindlin-2's scaffolding role. Reason: Membrane recruitment of adhesome partners is part of the core scaffolding function. |
| GO:0005654 nucleoplasm | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Nucleoplasmic localization (IDA/HPA) reflects the moonlighting nuclear pool involved in CTNNB1/TCF-mediated transcription; peripheral to the core adhesion role. Reason: Nuclear pool serving moonlighting transcriptional crosstalk, not the adhesion core. |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: Cytosolic pool (IDA/TAS) of kindlin-2 before/while it is recruited to membrane adhesion sites; consistent with a soluble cytoplasmic adapter. Reason: Soluble cytosolic pool of a cytoplasmic adhesion adapter. |
| GO:0005925 focal adhesion | IDA GO_REF:0000052 | ACCEPT | Summary: Focal adhesion is the defining subcellular site of kindlin-2, where it co-localizes with actin stress fibers at cell-ECM adhesions and recruits partners such as FBLIM1. Reason: Focal adhesion is the central, defining localization of kindlin-2. |
| GO:0035025 positive regulation of Rho protein signal transduction | IMP PMID:29496737 Kindlin-2 regulates mesenchymal stem cell differentiation th... | ACCEPT | Summary: Positively regulates Rho-family signaling (IMP) emanating from adhesion sites, coupling kindlin-2-mediated integrin engagement to actomyosin/stress-fiber regulation. Reason: Adhesion-coupled Rho signaling is integral to the integrin-to-cytoskeleton core role. |
| GO:0043539 protein serine/threonine kinase activator activity | IMP PMID:29496737 Kindlin-2 regulates mesenchymal stem cell differentiation th... | KEEP AS NON CORE | Summary: Reported activation of a Ser/Thr kinase (IMP) is a context-specific signaling output downstream of kindlin-2 adhesion scaffolding, not a defining enzymatic-partner activity. Reason: Downstream kinase-activation output, secondary to the integrin-adapter core. |
| GO:0120283 protein serine/threonine kinase binding | IPI PMID:29496737 Kindlin-2 regulates mesenchymal stem cell differentiation th... | KEEP AS NON CORE | Summary: Binding a Ser/Thr kinase (IPI), e.g. in TGF-beta-receptor-associated signaling, is a specific secondary partner interaction peripheral to the integrin-adhesion function. Reason: Specific kinase-partner binding tied to secondary signaling, not the adhesion core. |
| GO:0005515 protein binding | IPI PMID:25160619 Molecular basis of kindlin-2 binding to integrin-linked kina... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' (IPI) is uninformative for an adapter with many defined partners (integrins, FBLIM1, ILK, CTNNB1); specific binding terms already capture the meaningful interactions. Reason: Generic uninformative MF; specific partner-binding terms are preferable. |
| GO:0009898 cytoplasmic side of plasma membrane | IDA PMID:21325030 Kindlin-2 regulates podocyte adhesion and fibronectin matrix... | ACCEPT | Summary: Localizes to the cytoplasmic face of the plasma membrane (IDA), where it binds inner-leaflet phosphoinositides and integrin beta cytoplasmic tails; the precise site of its core action. Reason: Inner-leaflet membrane localization is the precise site of integrin-tail/PIP binding. |
| GO:0007155 cell adhesion | IGI PMID:21356350 Kindlin-1 and -2 have overlapping functions in epithelial ce... | ACCEPT | Summary: Kindlin-2 is required for integrin-mediated cell adhesion to the ECM (IGI/IMP); a core process directly arising from its integrin co-activation and focal-adhesion assembly activities. Reason: Cell adhesion is a core process directly mediated by kindlin-2. |
| GO:1900026 positive regulation of substrate adhesion-dependent cell spreading | IGI PMID:30254023 Kindlin-2 interacts with a highly conserved surface of ILK t... | ACCEPT | Summary: Promotes substrate-dependent cell spreading (IGI), requiring both integrin and phospholipid binding; a direct readout of kindlin-2 integrin co-activation at the leading edge. Reason: Spreading promotion is a direct core consequence of integrin co-activation. |
| GO:0033625 positive regulation of integrin activation | IGI PMID:21356350 Kindlin-1 and -2 have overlapping functions in epithelial ce... | ACCEPT | Summary: Positively regulates integrin activation by cooperating with talin at the beta-tail (IGI), the directional core activity by which kindlin-2 promotes integrin affinity. Reason: Positive integrin-activation regulation is the core kindlin-2 function. |
| GO:0048041 focal adhesion assembly | IMP PMID:21356350 Kindlin-1 and -2 have overlapping functions in epithelial ce... | ACCEPT | Summary: Kindlin-2 is required for focal-adhesion assembly; its integrin co-activation nucleates the adhesion complex, a core process supported by IMP/ISS evidence. Reason: Focal-adhesion assembly is a core process requiring kindlin-2. |
| GO:1903691 positive regulation of wound healing, spreading of epidermal cells | IMP PMID:21356350 Kindlin-1 and -2 have overlapping functions in epithelial ce... | KEEP AS NON CORE | Summary: Promotes epidermal-cell spreading in wound healing (IMP), an organismal/tissue phenotype downstream of kindlin-2-driven integrin adhesion and cell spreading. Reason: Wound-healing tissue phenotype downstream of the adhesion/spreading core. |
| GO:0005737 cytoplasm | IDA PMID:28799653 Kindlin-2 interacts with endothelial adherens junctions to s... | ACCEPT | Summary: Kindlin-2 is a cytoplasmic protein (IDA); consistent with its role as a cytosolic adapter recruited to membrane-proximal integrin tails and focal adhesions. Reason: Bulk cytoplasmic localization matches a cytoplasmic adhesion adapter. |
| GO:0005912 adherens junction | IDA PMID:28799653 Kindlin-2 interacts with endothelial adherens junctions to s... | KEEP AS NON CORE | Summary: Adherens-junction localization (IDA) reflects kindlin-2 at cell-cell adhesion sites in some epithelial contexts; secondary to its principal cell-matrix focal-adhesion localization. Reason: Cell-cell junction context is secondary to the core cell-matrix focal-adhesion site. |
| GO:0034334 adherens junction maintenance | IMP PMID:28799653 Kindlin-2 interacts with endothelial adherens junctions to s... | KEEP AS NON CORE | Summary: Kindlin-2 contributes to maintaining adherens junctions, a downstream tissue-integrity role distinct from its proximal integrin/focal-adhesion adapter activity. Reason: Downstream junction-maintenance process, not the proximal integrin-adhesion function. |
| GO:0043116 negative regulation of vascular permeability | IMP PMID:28799653 Kindlin-2 interacts with endothelial adherens junctions to s... | KEEP AS NON CORE | Summary: Reduces vascular permeability (IMP) via endothelial adhesion/junction integrity, a physiological consequence of kindlin-2 adhesion function rather than its proximal molecular role. Reason: Endothelial-barrier phenotype downstream of the core adhesion role. |
| GO:0005737 cytoplasm | IDA PMID:18528435 Colocalization of kindlin-1, kindlin-2, and migfilin at kera... | ACCEPT | Summary: Kindlin-2 is a cytoplasmic protein (IDA); consistent with its role as a cytosolic adapter recruited to membrane-proximal integrin tails and focal adhesions. Reason: Bulk cytoplasmic localization matches a cytoplasmic adhesion adapter. |
| GO:0005925 focal adhesion | IDA PMID:18528435 Colocalization of kindlin-1, kindlin-2, and migfilin at kera... | ACCEPT | Summary: Focal adhesion is the defining subcellular site of kindlin-2, where it co-localizes with actin stress fibers at cell-ECM adhesions and recruits partners such as FBLIM1. Reason: Focal adhesion is the central, defining localization of kindlin-2. |
| GO:0010718 positive regulation of epithelial to mesenchymal transition | IDA PMID:24226523 Kindlin-2 regulates renal tubular cell plasticity by activat... | KEEP AS NON CORE | Summary: Promotes EMT (IDA), likely via TGF-beta/Wnt crosstalk; a pleiotropic cell-state transition downstream of kindlin-2 adhesion and signaling roles. Reason: EMT promotion is downstream pleiotropic crosstalk, not the adhesion core. |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IDA PMID:24226523 Kindlin-2 regulates renal tubular cell plasticity by activat... | KEEP AS NON CORE | Summary: Promotes PI3K/AKT signaling (IDA), a downstream survival/growth cascade activated through integrin adhesion; a secondary signaling output of kindlin-2. Reason: Downstream PI3K/AKT signaling output of the adhesion core, not the proximal function. |
| GO:0070374 positive regulation of ERK1 and ERK2 cascade | IDA PMID:24226523 Kindlin-2 regulates renal tubular cell plasticity by activat... | KEEP AS NON CORE | Summary: Promotes ERK1/2 signaling (IDA) as a downstream consequence of integrin-mediated adhesion signaling; a secondary signaling output of the adhesion core. Reason: Downstream MAPK output of adhesion signaling, not the proximal adapter function. |
| GO:0005829 cytosol | IDA PMID:23723426 Kindlin-2 mediates activation of TGF-Ξ²/Smad signaling and re... | ACCEPT | Summary: Cytosolic pool (IDA/TAS) of kindlin-2 before/while it is recruited to membrane adhesion sites; consistent with a soluble cytoplasmic adapter. Reason: Soluble cytosolic pool of a cytoplasmic adhesion adapter. |
| GO:0005886 plasma membrane | IDA PMID:23723426 Kindlin-2 mediates activation of TGF-Ξ²/Smad signaling and re... | ACCEPT | Summary: Plasma-membrane localization (IDA) is where kindlin-2 binds integrin beta tails and inner-leaflet phosphoinositides; consistent with its membrane-proximal adapter role. Reason: Plasma-membrane localization is core to integrin-tail and lipid engagement. |
| GO:0034713 type I transforming growth factor beta receptor binding | IPI PMID:23723426 Kindlin-2 mediates activation of TGF-Ξ²/Smad signaling and re... | KEEP AS NON CORE | Summary: Binding the type I TGF-beta receptor (IPI) supports kindlin-2's modulation of TGF-beta/SMAD signaling; a specific partner in a pleiotropic pathway, not the adhesion core. Reason: Specific TGF-beta receptor partner underlying pleiotropic signaling, peripheral to adhesion. |
| GO:0046332 SMAD binding | IPI PMID:23723426 Kindlin-2 mediates activation of TGF-Ξ²/Smad signaling and re... | KEEP AS NON CORE | Summary: SMAD binding (IPI) underlies kindlin-2 participation in TGF-beta/SMAD crosstalk; a secondary signaling partner, peripheral to its integrin-adapter core. Reason: Pleiotropic TGF-beta signaling partner, not part of the proximal integrin-adhesion function. |
| GO:1900182 positive regulation of protein localization to nucleus | IDA PMID:23723426 Kindlin-2 mediates activation of TGF-Ξ²/Smad signaling and re... | KEEP AS NON CORE | Summary: Promotes nuclear localization of a partner (e.g. beta-catenin, IDA), part of kindlin-2's moonlighting transcriptional role; distinct from its cytoplasmic adhesion function. Reason: Nuclear-trafficking role tied to moonlighting transcription, peripheral to adhesion. |
| GO:0003779 actin binding | IMP PMID:29496737 Kindlin-2 regulates mesenchymal stem cell differentiation th... | ACCEPT | Summary: Kindlin-2 binds actin, contributing to the physical connection between integrin-based ECM adhesion sites and the actin cytoskeleton; central to its cytoskeletal-linker adapter role. Reason: Direct actin binding is part of the defining integrin-to-actin linkage function. |
| GO:0005925 focal adhesion | IDA PMID:29496737 Kindlin-2 regulates mesenchymal stem cell differentiation th... | ACCEPT | Summary: Focal adhesion is the defining subcellular site of kindlin-2, where it co-localizes with actin stress fibers at cell-ECM adhesions and recruits partners such as FBLIM1. Reason: Focal adhesion is the central, defining localization of kindlin-2. |
| GO:0019901 protein kinase binding | IPI PMID:30254023 Kindlin-2 interacts with a highly conserved surface of ILK t... | ACCEPT | Summary: Kindlin-2 binds protein kinase partners (e.g. ILK within the kindlin-ILK-PINCH/IPP focal-adhesion complex), a specific interaction central to assembling the integrin adhesome. Reason: Specific kinase (ILK/adhesome) binding is part of the core focal-adhesion scaffolding role. |
| GO:0022604 regulation of cell morphogenesis | IMP PMID:30254023 Kindlin-2 interacts with a highly conserved surface of ILK t... | ACCEPT | Summary: Regulates cell morphogenesis/shape (IMP) via orchestration of actin assembly at integrin adhesions; cell-shape modulation is an intrinsic part of kindlin-2's described function. Reason: Cell-shape/morphogenesis modulation is an intrinsic core kindlin-2 function. |
| GO:0045599 negative regulation of fat cell differentiation | IMP PMID:29496737 Kindlin-2 regulates mesenchymal stem cell differentiation th... | KEEP AS NON CORE | Summary: Inhibits adipocyte differentiation (IMP), a cell-fate output of kindlin-2 adhesion/signaling crosstalk, downstream and tissue-specific relative to the integrin-adapter core. Reason: Cell-differentiation output downstream of adhesion signaling, not the core function. |
| GO:0045669 positive regulation of osteoblast differentiation | IMP PMID:29496737 Kindlin-2 regulates mesenchymal stem cell differentiation th... | KEEP AS NON CORE | Summary: Promotes osteoblast differentiation (IMP), a skeletal cell-fate output linked to integrin/fibronectin adhesion; downstream and tissue-specific relative to the adapter core. Reason: Tissue-specific differentiation output downstream of integrin adhesion. |
| GO:0051496 positive regulation of stress fiber assembly | IMP PMID:29496737 Kindlin-2 regulates mesenchymal stem cell differentiation th... | ACCEPT | Summary: Promotes stress-fiber assembly (IMP) by coupling integrin adhesions to actin, reflecting kindlin-2's integrin-to-cytoskeleton linkage and cell-shape modulation. Reason: Stress-fiber promotion follows directly from the integrin-actin linker role. |
| GO:0051894 positive regulation of focal adhesion assembly | IMP PMID:29496737 Kindlin-2 regulates mesenchymal stem cell differentiation th... | ACCEPT | Summary: Promotes focal-adhesion assembly (IMP) as a direct consequence of kindlin-2-driven integrin activation and adhesome recruitment; a core adhesion process. Reason: Promoting focal-adhesion assembly is part of the core adhesion function. |
| GO:1902414 protein localization to cell junction | IMP PMID:30254023 Kindlin-2 interacts with a highly conserved surface of ILK t... | KEEP AS NON CORE | Summary: Targets partner proteins (e.g. FBLIM1) to adhesion junctions (IMP); a specific recruitment activity supporting, but downstream of, the proximal integrin-adapter role. Reason: Partner-recruitment-to-junction activity downstream of the core scaffolding function. |
| GO:1902462 positive regulation of mesenchymal stem cell proliferation | IMP PMID:29496737 Kindlin-2 regulates mesenchymal stem cell differentiation th... | KEEP AS NON CORE | Summary: Promotes MSC proliferation (IMP), a cell-type-specific growth output of kindlin-2 adhesion/signaling activity, downstream of its proximal integrin-adapter role. Reason: Cell-type-specific proliferation output downstream of adhesion function. |
| GO:0005886 plasma membrane | IDA PMID:30382829 Fermitin family homolog-2 (FERMT2) is highly expressed in hu... | ACCEPT | Summary: Plasma-membrane localization (IDA) is where kindlin-2 binds integrin beta tails and inner-leaflet phosphoinositides; consistent with its membrane-proximal adapter role. Reason: Plasma-membrane localization is core to integrin-tail and lipid engagement. |
| GO:0007155 cell adhesion | IMP PMID:30382829 Fermitin family homolog-2 (FERMT2) is highly expressed in hu... | ACCEPT | Summary: Kindlin-2 is required for integrin-mediated cell adhesion to the ECM (IGI/IMP); a core process directly arising from its integrin co-activation and focal-adhesion assembly activities. Reason: Cell adhesion is a core process directly mediated by kindlin-2. |
| GO:0030054 cell junction | IDA PMID:30382829 Fermitin family homolog-2 (FERMT2) is highly expressed in hu... | KEEP AS NON CORE | Summary: Generic cell-junction localization (IDA); kindlin-2's specific and defining junction is the cell-matrix focal adhesion, captured by more precise terms. Reason: Generic junction term subsumed by the specific focal-adhesion localization. |
| GO:0030335 positive regulation of cell migration | IMP PMID:30382829 Fermitin family homolog-2 (FERMT2) is highly expressed in hu... | KEEP AS NON CORE | Summary: Promotes cell migration (IMP), a downstream behavior enabled by kindlin-2-driven focal-adhesion dynamics and integrin activation rather than a defining molecular function. Reason: Migration is a downstream cellular behavior of the integrin-adhesion core. |
| GO:0005925 focal adhesion | IDA PMID:29162887 The WD40-domain containing protein CORO2B is specifically en... | ACCEPT | Summary: Focal adhesion is the defining subcellular site of kindlin-2, where it co-localizes with actin stress fibers at cell-ECM adhesions and recruits partners such as FBLIM1. Reason: Focal adhesion is the central, defining localization of kindlin-2. |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | ACCEPT | Summary: Focal adhesion is the defining subcellular site of kindlin-2, where it co-localizes with actin stress fibers at cell-ECM adhesions and recruits partners such as FBLIM1. Reason: Focal adhesion is the central, defining localization of kindlin-2. |
| GO:0005829 cytosol | TAS Reactome:R-HSA-430341 | ACCEPT | Summary: Cytosolic pool (IDA/TAS) of kindlin-2 before/while it is recruited to membrane adhesion sites; consistent with a soluble cytoplasmic adapter. Reason: Soluble cytosolic pool of a cytoplasmic adhesion adapter. |
| GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding | IDA PMID:21325030 Kindlin-2 regulates podocyte adhesion and fibronectin matrix... | ACCEPT | Summary: The PH domain binds PIP3 preferentially (NMR structure, PMID:22030399); K383/K385 mutations reduce lipid binding and integrin activation, making this lipid-binding activity core to membrane targeting. Reason: PH-domain PIP3 binding is mechanistically required for membrane-proximal integrin activation. |
| GO:0005634 nucleus | IDA PMID:22699938 Kindlin 2 forms a transcriptional complex with Ξ²-catenin and... | KEEP AS NON CORE | Summary: Nuclear localization underlies kindlin-2's moonlighting role in Wnt/beta-catenin transcriptional regulation; distinct from its principal cytoplasmic focal-adhesion function. Reason: Secondary nuclear/transcriptional role, separate from the core integrin-adhesion function. |
| GO:0005737 cytoplasm | IDA PMID:22699938 Kindlin 2 forms a transcriptional complex with Ξ²-catenin and... | ACCEPT | Summary: Kindlin-2 is a cytoplasmic protein (IDA); consistent with its role as a cytosolic adapter recruited to membrane-proximal integrin tails and focal adhesions. Reason: Bulk cytoplasmic localization matches a cytoplasmic adhesion adapter. |
| GO:0005925 focal adhesion | IDA PMID:21325030 Kindlin-2 regulates podocyte adhesion and fibronectin matrix... | ACCEPT | Summary: Focal adhesion is the defining subcellular site of kindlin-2, where it co-localizes with actin stress fibers at cell-ECM adhesions and recruits partners such as FBLIM1. Reason: Focal adhesion is the central, defining localization of kindlin-2. |
| GO:0007160 cell-matrix adhesion | IMP PMID:21325030 Kindlin-2 regulates podocyte adhesion and fibronectin matrix... | ACCEPT | Summary: Enhances integrin-mediated cell adhesion onto the extracellular matrix, requiring both integrin and phospholipid binding; the precise adhesion process at kindlin-2's core. Reason: Cell-matrix adhesion is the defining biological process of kindlin-2. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IMP PMID:21325030 Kindlin-2 regulates podocyte adhesion and fibronectin matrix... | KEEP AS NON CORE | Summary: Participates in TGF-beta receptor signaling (IMP) via receptor/SMAD interactions; a pleiotropic signaling role distinct from the integrin-adhesion core. Reason: Pleiotropic TGF-beta signaling role, separate from the core adhesion function. |
| GO:0007229 integrin-mediated signaling pathway | IMP PMID:21325030 Kindlin-2 regulates podocyte adhesion and fibronectin matrix... | ACCEPT | Summary: Initiates/propagates integrin-mediated (inside-out and outside-in) signaling through integrin-tail engagement and adhesome assembly; a core signaling process for kindlin-2. Reason: Integrin signaling is a core pathway directly engaged by kindlin-2. |
| GO:0016055 Wnt signaling pathway | IMP PMID:22699938 Kindlin 2 forms a transcriptional complex with Ξ²-catenin and... | KEEP AS NON CORE | Summary: Kindlin-2 stabilizes active CTNNB1 and forms a complex with CTNNB1/TCF7L2 to enhance Wnt-driven transcription (PMID:22699938); a moonlighting nuclear role distinct from focal-adhesion adhesion. Reason: Nuclear Wnt/beta-catenin crosstalk is a pleiotropic moonlighting role, not the core adhesion function. |
| GO:0005547 phosphatidylinositol-3,4,5-trisphosphate binding | IDA PMID:22030399 Structural basis of phosphoinositide binding to kindlin-2 pr... | ACCEPT | Summary: The PH domain binds PIP3 preferentially (NMR structure, PMID:22030399); K383/K385 mutations reduce lipid binding and integrin activation, making this lipid-binding activity core to membrane targeting. Reason: PH-domain PIP3 binding is mechanistically required for membrane-proximal integrin activation. |
| GO:0007160 cell-matrix adhesion | ISS GO_REF:0000024 | ACCEPT | Summary: Enhances integrin-mediated cell adhesion onto the extracellular matrix, requiring both integrin and phospholipid binding; the precise adhesion process at kindlin-2's core. Reason: Cell-matrix adhesion is the defining biological process of kindlin-2. |
| GO:0033622 integrin activation | IMP PMID:22030399 Structural basis of phosphoinositide binding to kindlin-2 pr... | ACCEPT | Summary: Co-activates integrins with talin: binding the membrane-distal beta-tail NPxY motif, kindlin-2 enhances affinity maturation; QW614-615AA abolishes ITGB3 binding and activation enhancement. Reason: Integrin (co-)activation is the central molecular process defining kindlin-2. |
| GO:0034446 substrate adhesion-dependent cell spreading | ISS GO_REF:0000024 | ACCEPT | Summary: Mediates substrate adhesion-dependent cell spreading (ISS); kindlin-2 enhancement of ECM adhesion and lamellipodial integrin engagement drives cell spreading. Reason: Substrate-dependent spreading is a core process driven by kindlin-2 adhesion activity. |
| GO:0048041 focal adhesion assembly | ISS GO_REF:0000024 | ACCEPT | Summary: Kindlin-2 is required for focal-adhesion assembly; its integrin co-activation nucleates the adhesion complex, a core process supported by IMP/ISS evidence. Reason: Focal-adhesion assembly is a core process requiring kindlin-2. |
| GO:0072657 protein localization to membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Recruits/retains partners at the plasma membrane (ISS) as part of assembling the membrane-proximal integrin adhesion complex; integral to kindlin-2's scaffolding role. Reason: Membrane recruitment of adhesome partners is part of the core scaffolding function. |
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Download this section (compressed HTML)Q: Which FERMT2 pathway outputs should be treated as general kindlin-2 biology versus cell-type-specific consequences of integrin/focal-adhesion scaffolding?
Q: Does Alzheimer-associated FERMT2 biology act through brain vascular barrier, microglial adhesion/migration, synaptic extracellular-matrix responses, or a different cell type?
Q: Can partner-specific annotations replace remaining generic or context-dependent interaction terms after full-text review of the source papers?
Experiment: Perturb FERMT2 in human iPSC-derived endothelial cells, pericytes, astrocytes, and microglia, then quantify integrin activation, focal-adhesion dynamics, barrier integrity, migration, and extracellular-matrix responses under amyloid or inflammatory stress.
Hypothesis: FERMT2 Alzheimer relevance depends on integrin/focal-adhesion regulation in vascular or glial cell adhesion states.
Type: cell-type-specific adhesion and barrier assay
Experiment: Compare wild-type FERMT2 with PH-domain phosphoinositide-binding mutants in endogenous rescue assays measuring PIP3-dependent membrane recruitment, talin cooperation, integrin activation, focal-adhesion assembly, and cell spreading.
Hypothesis: FERMT2 phosphoinositide binding controls integrin activation by recruiting kindlin-2 to PIP3-rich adhesion membranes.
Type: structure-function rescue assay
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