GMFB

GO Term	Evidence	Action	Reason
GO:0071933 Arp2/3 complex binding	IBA GO_REF:0000033	ACCEPT	Summary: Arp2/3 complex binding is the most specific molecular-function annotation for GMFB's conserved GMF-family activity. Reason: Falcon research supports GMFB as an Arp2/3-centered actin-network remodeling factor rather than a generic actin-binding or growth-factor protein. Supporting Evidence: file:human/GMFB/GMFB-deep-research-falcon.md Current consensus from the cited review and recent primary work is that GMF-beta is an actin-network remodeling factor that binds the Arp2/3 complex
GO:0030864 cortical actin cytoskeleton	IBA GO_REF:0000033	ACCEPT	Summary: Cortical/leading-edge branched actin structures are an appropriate active site for GMFB-mediated actin network remodeling. Reason: The location is supported by the biology of Arp2/3-branched actin networks even though the direct microscopy evidence in the falcon report is mostly from cell-context studies. Supporting Evidence: file:human/GMFB/GMFB-deep-research-falcon.md its described mechanism--binding Arp2/3, regulating lamellipodial/leading-edge dynamics--places its primary functional locus at cytoskeletal actin networks enriched for Arp2/3-dependent branching
GO:0071846 actin filament debranching	IBA GO_REF:0000033	ACCEPT	Summary: Actin filament debranching is a specific and conserved GMF-family biological process. Reason: This annotation captures GMFB's direct contribution to turnover of Arp2/3-branched actin arrays. Supporting Evidence: file:human/GMFB/GMFB-deep-research-falcon.md stimulates debranching of branched actin filament networks
GO:0034316 negative regulation of Arp2/3 complex-mediated actin nucleation	IBA GO_REF:0000033	ACCEPT	Summary: GMFB negatively regulates Arp2/3-mediated nucleation as part of its branched-actin remodeling mechanism. Reason: This term is mechanistically specific and complements the debranching annotation. Supporting Evidence: file:human/GMFB/GMFB-deep-research-falcon.md inhibits Arp2/3-driven actin nucleation/branch formation
GO:0007165 signal transduction	IEA GO_REF:0000108	MARK AS OVER ANNOTATED	Summary: GMFB can influence signaling pathways downstream of actin remodeling, but the broad signal-transduction annotation is indirect and likely derived from legacy growth-factor/activity links. Reason: The current core function is Arp2/3-branched actin remodeling; signaling effects such as Ca2+-NFAT or inflammatory pathway changes are downstream cellular outcomes rather than a primary GO process for GMFB. Supporting Evidence: file:human/GMFB/GMFB-deep-research-falcon.md the most direct mechanistic chain supported in the evidence is GMFB to actin remodeling to Ca2+ to calcineurin to NFATc2
GO:0003779 actin binding	IEA GO_REF:0000002	MODIFY	Summary: The ADF-H domain places GMFB in actin-network biology, but the more precise molecular-function annotation is Arp2/3 complex binding. Reason: Falcon research explicitly notes that GMFB does not primarily bind actin directly and instead acts through Arp2/3. Proposed replacements: Arp2/3 complex binding Supporting Evidence: file:human/GMFB/GMFB-deep-research-falcon.md unlike canonical ADF/cofilins--does not primarily bind actin directly, and instead acts mainly through the Arp2/3 complex
GO:0008083 growth factor activity	IEA GO_REF:0000043	REMOVE	Summary: The growth factor activity annotation reflects the historical protein name and early biological activity assays rather than a current mechanistic molecular function. Reason: There is no strong evidence here that GMFB is a secreted growth factor in the GO molecular-function sense; its supported core role is intracellular Arp2/3/actin network remodeling. Supporting Evidence: file:human/GMFB/GMFB-uniprot.txt Belongs to the actin-binding proteins ADF family. GMF subfamily.
GO:0071846 actin filament debranching	IEA GO_REF:0000002	ACCEPT	Summary: The InterPro2GO debranching annotation agrees with the IBA annotation and the falcon-summarized GMF-family mechanism. Reason: Actin filament debranching is a specific, supported biological process for GMFB. Supporting Evidence: file:human/GMFB/GMFB-deep-research-falcon.md GMF-beta controls branched actin content and lamellipodial dynamics in fibroblasts
GO:0071933 Arp2/3 complex binding	IEA GO_REF:0000002	ACCEPT	Summary: The InterPro2GO Arp2/3 binding annotation is consistent with stronger IBA evidence and current GMFB literature. Reason: This is the most informative molecular-function term in the GMFB GOA file. Supporting Evidence: file:human/GMFB/GMFB-deep-research-falcon.md Foundational primary work cited in the review describes GMF as a cofilin homolog that binds Arp2/3
GO:0004860 protein kinase inhibitor activity	TAS PMID:8639570 In vitro inhibition of MAP kinase (ERK1/ERK2) activity by ph...	MODIFY	Summary: The cited in vitro study supports phosphorylated GMF inhibiting ERK1/2, but the broad kinase inhibitor term should be replaced with the more specific serine/threonine kinase inhibitor activity term. Reason: ERK1/2 are protein serine/threonine kinases, so the specific replacement term preserves the direct in vitro observation without elevating this historical MAPK effect above GMFB's current core Arp2/3-dependent actin remodeling function. Proposed replacements: protein serine/threonine kinase inhibitor activity Supporting Evidence: PMID:8639570 recombinant glia maturation factor (GMF), a 17-kDa brain protein, inhibits the activity of mitogen-activated protein (MAP) kinase in the test tube assay
GO:0006468 protein phosphorylation	TAS PMID:7598724 Phorbol ester stimulates rapid intracellular phosphorylation...	REMOVE	Summary: This is a substrate/process misannotation: the cited paper describes GMF being phosphorylated by kinases, not GMFB catalyzing protein phosphorylation. Reason: GMFB is not a kinase; phosphorylation of GMFB is a post-translational modification of GMFB, not a biological process carried out by GMFB. Supporting Evidence: PMID:7598724 recombinant glia maturation factor (GMF), a 17-kD brain protein, can be phosphorylated in vitro at the serine residue by protein kinase C (PKC), protein kinase A (PKA), and casein kinase II (CKII)
GO:0007399 nervous system development	TAS PMID:1712830 Molecular cloning and expression of biologically active huma...	KEEP AS NON CORE	Summary: Early GMFB work supports biological activity in neural/glial contexts, but nervous system development is broad relative to the current mechanistic understanding. Reason: Retain as a historical non-core process association, while core function should focus on Arp2/3/actin remodeling. Supporting Evidence: PMID:1712830 Glia maturation factor-beta, a protein found in the brains of all vertebrates thus far examined, appears to play a role in the differentiation, maintenance, and regeneration of the nervous system.
GO:0008047 enzyme activator activity	TAS PMID:8798479 In vitro enhancement of p38 mitogen-activated protein kinase...	MODIFY	Summary: The cited in vitro study supports phosphorylated GMF enhancing p38 MAP kinase activity, but the broad enzyme activator term should be replaced with the specific protein serine/threonine kinase activator term. Reason: p38 MAP kinase is a protein serine/threonine kinase, so the specific replacement term captures the direct in vitro result while leaving Arp2/3-dependent actin remodeling as the core function. Proposed replacements: protein serine/threonine kinase activator activity Supporting Evidence: PMID:8798479 PKA-phosphorylated GMF strongly enhances the activity of a related but distinct subfamily of MAP kinase, the p38 MAP kinase

Deep Research

Falcon

(GMFB-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 23 citations 2026-05-02T22:02:58.636882

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

We are interested in where in or outside the cell the gene product carries out its function.

We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Human GMFB (Glia maturation factor beta; GMF-β)

1) Verification of gene/protein identity (critical disambiguation)

The literature retrieved here consistently maps GMF-β / GMFB to human glia maturation factor beta with UniProt accession P60983, a small (~141 aa; ~14–17 kDa) protein in the ADF-H (actin-depolymerizing factor homology) / ADF-cofilin superfamily. (shishkin2016cofilin1andother pages 3-5, xu2024glialmaturationfactorβ pages 1-2)

A key point for functional annotation is that GMF-β is described as an ADF-H fold protein that—unlike canonical ADF/cofilins—does not primarily bind actin directly, and instead acts mainly through the Arp2/3 complex. (shishkin2016cofilin1andother pages 5-7, shishkin2016cofilin1andother pages 3-5)

2) Key concepts, definitions, and current mechanistic understanding

2.1 Core molecular function: Arp2/3-directed remodeling of branched actin

Current consensus from the cited review and recent primary work is that GMF-β is an actin-network remodeling factor that binds the Arp2/3 complex and thereby:
- inhibits Arp2/3-driven actin nucleation/branch formation, and
- stimulates debranching of branched actin filament networks. (shishkin2016cofilin1andother pages 22-24, xu2024glialmaturationfactorβ pages 11-12, shishkin2016cofilin1andother pages 7-9, xu2024glialmaturationfactorβ pages 1-2)

Mechanistically, this positions GMF-β as a regulator of branched actin turnover at protrusive structures (e.g., lamellipodia/leading edge) rather than as an actin-severing/depolymerizing enzyme per se. Foundational primary work cited in the review describes GMF as a cofilin homolog that binds Arp2/3 to stimulate debranching and inhibit nucleation, and further reports that GMFβ controls branched actin content and lamellipodial dynamics in fibroblasts. (shishkin2016cofilin1andother pages 22-24)

2.2 Domain/structure-level inference relevant to function

GMF proteins contain a single ADF-H domain; NMR studies summarized in the review report that GMF ADF-H domains possess two additional β-strands in a loop compared with other ADF-H classes, proposed as a class-defining feature that may relate to their distinct Arp2/3-centered mechanism. (shishkin2016cofilin1andother pages 3-5, shishkin2016cofilin1andother pages 5-7)

3) Cellular localization, expression context, and pathway placement

3.1 Expression context

GMFB is described as primarily isolated from astrocytes, but also expressed across diverse organs/tissues, and in the CNS is expressed by neuronal and glial cells. (xu2024glialmaturationfactorβ pages 11-12, amlerova2024reactivegliosisin pages 15-16)

3.2 Subcellular locus of action (inferred from function)

Although the retrieved sources do not provide a definitive microscopy-based statement of subcellular compartment (e.g., cytosol vs. specific membrane subdomains) for human GMF-β, its described mechanism—binding Arp2/3, regulating lamellipodial/leading-edge dynamics—places its primary functional locus at cytoskeletal actin networks enriched for Arp2/3-dependent branching, such as lamellipodia and other branched actin arrays. (shishkin2016cofilin1andother pages 7-9, shishkin2016cofilin1andother pages 22-24)

3.3 Pathway links (signaling coupled to cytoskeletal remodeling)

Recent work in bone marrow mesenchymal stem cells (BMSCs) links GMFB-mediated actin remodeling to intracellular signaling:
- GMFB knockout increases F-actin formation/intensity and alters filament organization and recovery after latrunculin B washout, consistent with removing an Arp2/3 debranching/anti-polymerization activity. (xu2024glialmaturationfactorβ pages 7-9)
- GMFB-dependent cytoskeletal state is linked to intracellular Ca2+ and downstream calcineurin–NFATc2 signaling: GMFB loss increases cytoplasmic Ca2+ and promotes NFATc2 nuclear translocation; cyclosporin A blocks NFATc2 translocation and reverses the anti-adipogenic effect of GMFB knockout. (xu2024glialmaturationfactorβ pages 12-13, xu2024glialmaturationfactorβ pages 7-9)
- Pathway analyses in this system implicate broader signaling changes (e.g., effects on MAPK/Wnt/PPAR signaling), but the most direct mechanistic chain supported in the evidence is GMFB → actin remodeling → Ca2+ → calcineurin → NFATc2. (xu2024glialmaturationfactorβ pages 9-11, xu2024glialmaturationfactorβ pages 7-9)

In neuroinflammatory contexts (TBI/reactive gliosis), a 2024 comprehensive review summarizes evidence that GMFB can activate p38 and NF-κB pathways (with some ERK involvement), and that GMFB deletion reduces inflammatory mediators and NF-κB phosphorylation in vivo. (amlerova2024reactivegliosisin pages 15-16)

4) Recent developments (prioritizing 2023–2024)

4.1 2024: GMFB in osteoporosis pathophysiology via actin/Ca2+/NFAT

A 2024 primary study in Cell Death & Disease reports that GMFB expression is increased in bone tissue from ovariectomized (OVX) rats and postmenopausal osteoporosis (PMOP) patients, and that GMFB knockout reduces bone marrow adipocyte accumulation and increases bone mass in OVX models, with mechanistic dependence on actin remodeling and Ca2+-calcineurin–NFATc2 signaling. (xu2024glialmaturationfactorβ pages 1-2, xu2024glialmaturationfactorβ pages 12-13)

4.2 2024: GMFB in traumatic brain injury (reactive gliosis/neuroinflammation)

A 2024 review summarizes that GMFB protein increases after TBI (detectable by 1 day post-injury, peaking at 14 days), with mRNA elevated by 7 days (peak 14 days). The same review describes that GMFB deletion reduces lesion volume, inhibits gliosis, increases neuronal survival, shifts microglia toward anti-inflammatory polarization, and reduces NF-κB phosphorylation and inflammatory mediators (e.g., TNF-α, IL-6), while increasing anti-inflammatory cytokines (IL-4, IL-10). (amlerova2024reactivegliosisin pages 15-16)

4.3 2023: Human CSF proteomics places GMFB among early ADAD-associated changes

A 2023 Nature Medicine study measuring 59 CSF proteins by SRM-MS in autosomal dominant Alzheimer’s disease (ADAD) reports that 33/59 proteins differed significantly between mutation carriers and noncarriers at a 99% credible interval, and describes GMFB elevation during an early glycolytic/metabolic phase peaking at approximately −17 estimated years to onset (EYO), with levels later rising again around symptom onset. (johnson2023cerebrospinalfluidproteomics pages 3-4)

The paper’s proposed biomarker cascade places GMFB in module M14 and Category 2, and the cascade figure includes a plotted significance metric (a -log2(p) axis) with GMFB shown at approximately 10 on that scale; this is a measure of statistical support rather than an effect size. (johnson2023cerebrospinalfluidproteomics pages 5-6, johnson2023cerebrospinalfluidproteomics media a8d85915)

4.4 2023: GMFB proposed in early diabetic retinopathy mechanism involving lysosome/ferroptosis

A 2023 review in Frontiers in Endocrinology states that individuals with early diabetic retinopathy have elevated GMFB levels in vitreous, and proposes that abundant GMFB in a high-glucose environment may divert ATP6V1A from lysosomes, disrupt lysosomal assembly and alkalize lysosomes in retinal pigment epithelial (RPE) cells, thereby impairing chaperone-mediated autophagy (CMA) degradation of ACSL4 and promoting lipid peroxidation/ferroptosis. (sun2023theidealtreatment pages 11-12)

5) Current applications and real-world implementations

5.1 Biomarker development (research/clinical-translation stage)

Alzheimer’s disease: GMFB is included among CSF proteins that change across decades in ADAD, supporting its potential use as part of a multiplex CSF proteomic biomarker panel (research setting). (johnson2023cerebrospinalfluidproteomics pages 3-4, johnson2023cerebrospinalfluidproteomics pages 5-6)
Diabetic retinopathy: GMFB is discussed as elevated in vitreous early in disease and connected to an RPE lysosomal/ferroptosis mechanism, indicating potential as a candidate ocular-fluid biomarker or mechanistic marker (research setting). (sun2023theidealtreatment pages 11-12)

5.2 Therapeutic targeting (preclinical proof-of-concept)

Osteoporosis model: In vivo GMFB suppression using shRNA (including rAAV9-shRNA approaches described in the study) had favorable effects on OVX-induced bone loss, supporting GMFB as a candidate target in preclinical osteoporosis intervention strategies. (xu2024glialmaturationfactorβ pages 12-13, xu2024glialmaturationfactorβ pages 11-12)
AD precision strategies (preprint): A 2023 preprint reports GMFB is modulated by a brain-penetrant G9a inhibitor (MS1262) in AD models and that GMFB is considered G9a-regulated in the context of AD-associated proteomic changes; this remains pre-peer-review and is best viewed as hypothesis-generating for therapeutic positioning. (chen2023novelbrainpenetrantinhibitor pages 16-18, chen2023novelbrainpenetrantinhibitor pages 11-14)

6) Expert synthesis / authoritative interpretation (evidence-grounded)

Across mechanistic and disease-oriented sources, GMFB is best annotated as a non-enzymatic actin network regulator whose primary biochemical role is Arp2/3 complex regulation (branch inhibition and debranching), enabling control of branched actin architecture and dynamics. (shishkin2016cofilin1andother pages 22-24, xu2024glialmaturationfactorβ pages 11-12)

A unifying interpretation of the 2023–2024 literature is that GMFB can couple cytoskeletal remodeling to disease-relevant signaling programs:
- in mesenchymal stem cells, actin-state changes translate into Ca2+-dependent transcriptional control (NFATc2) that reprograms differentiation (adipogenesis vs. osteogenesis-related outcomes), (xu2024glialmaturationfactorβ pages 12-13, xu2024glialmaturationfactorβ pages 7-9)
- while in CNS injury models, GMFB is positioned as a pro-inflammatory regulator linked to p38/NF-κB, with temporal induction after injury and measurable effects on gliosis/neuroinflammation. (amlerova2024reactivegliosisin pages 15-16)

7) Key statistics and quantitative data from recent studies

ADAD CSF proteomics (2023, Nature Medicine): 59 CSF proteins measured by SRM-MS; 33 proteins significantly different (99% credible interval). GMFB is described as elevated in an early metabolic phase peaking around −17 EYO. (johnson2023cerebrospinalfluidproteomics pages 3-4)
ADAD cascade placement (2023): GMFB assigned to module M14 and Category 2; figure shows an approximate -log2(p) value around 10 for carriers vs. noncarriers (significance indicator, not effect size). (johnson2023cerebrospinalfluidproteomics pages 5-6, johnson2023cerebrospinalfluidproteomics media a8d85915)
TBI time-course (summarized in 2024 review): GMFB protein increased by 1 day post-injury and peaked at 14 days; GMFB mRNA elevated by 7 days, peak at 14 days. (amlerova2024reactivegliosisin pages 15-16)
Early DR (2023 review): patients with early DR show elevated vitreous GMFB; review proposes lysosome/CMA/ferroptosis mechanism. (sun2023theidealtreatment pages 11-12)
Actin phenotype (2024 Cell Death & Disease): GMFB knockout significantly increases F-actin mean intensity and produces longer, more ordered actin filaments; KO cells show greater actin recovery after latrunculin B washout. (xu2024glialmaturationfactorβ pages 7-9)

Evidence summary table

The following table consolidates supported functional-annotation evidence, emphasizing 2023–2024 findings while anchoring to foundational mechanistic sources.

Aspect	Key findings	Key evidence	Year	Publication/URL
identity/domains	GMFB was verified as human glia maturation factor beta (UniProt P60983), a small (~141 aa; ~14–17 kDa) ADF-H superfamily protein with a single ADF-H domain. Unlike canonical cofilins, reviewed evidence describes GMF-B as not primarily binding actin directly. (shishkin2016cofilin1andother pages 5-7, shishkin2016cofilin1andother pages 3-5, xu2024glialmaturationfactorβ pages 1-2, shishkin2016cofilin1andother pages 1-3)	Review/synthesis of domain classification and protein annotation; includes UniProt-linked identification and NMR-based structural description of GMF ADF-H domains, including two extra β-strands relative to other ADF-H classes. (shishkin2016cofilin1andother pages 3-5, shishkin2016cofilin1andother pages 5-7)	2016, 2024	Shishkin et al., Int J Mol Sci (2016), https://doi.org/10.3390/ijms18010010; Xu et al., Cell Death & Disease (2024), https://doi.org/10.1038/s41419-024-07234-z
molecular mechanism	The core annotated function is regulation of branched actin networks through Arp2/3: GMFB binds Arp2/3, stimulates filament debranching, and inhibits actin nucleation/polymerization. This mechanism is linked to control of branched actin content, lamellipodial dynamics, and leading-edge behavior. (shishkin2016cofilin1andother pages 22-24, xu2024glialmaturationfactorβ pages 11-12, shishkin2016cofilin1andother pages 7-9, xu2024glialmaturationfactorβ pages 1-2)	Foundational primary studies are cited in review as showing Arp2/3 binding/debranching and effects on lamellipodia/migration; recent 2024 experimental work used LC-MS/MS, phalloidin staining, and latrunculin B depolymerization/repolymerization assays to show that GMFB knockout increases F-actin intensity and alters filament architecture/recovery in BMSCs. (xu2024glialmaturationfactorβ pages 7-9, xu2024glialmaturationfactorβ pages 11-12, shishkin2016cofilin1andother pages 22-24)	2016, 2024	Shishkin et al., Int J Mol Sci (2016), https://doi.org/10.3390/ijms18010010; Xu et al., Cell Death & Disease (2024), https://doi.org/10.1038/s41419-024-07234-z
cellular localization/expression	GMFB is described as primarily isolated from astrocytes and expressed in neuronal and glial cells, with broader expression across diverse organs/tissues. In disease-associated contexts it is increased in OVX rat and PMOP bone tissue, and the 2024 bone study reports colocalization with BMSCs in OVX rats. (xu2024glialmaturationfactorβ pages 11-12, xu2024glialmaturationfactorβ pages 1-2, amlerova2024reactivegliosisin pages 15-16)	Review evidence summarizes tissue/cell-type expression; recent primary work used tissue immunostaining and bone samples from rats/patients to detect increased GMFB expression and localization in bone/BMSCs under osteoporotic conditions. TBI review also summarizes temporal upregulation after injury. (xu2024glialmaturationfactorβ pages 1-2, xu2024glialmaturationfactorβ pages 11-12, amlerova2024reactivegliosisin pages 15-16)	2024	Xu et al., Cell Death & Disease (2024), https://doi.org/10.1038/s41419-024-07234-z; Amlerova et al., Front Cell Neurosci (2024), https://doi.org/10.3389/fncel.2024.1335849
pathway links	Beyond cytoskeletal remodeling, GMFB is linked to Ca2+-calcineurin-NFATc2 signaling in BMSCs, where GMFB loss enhances F-actin and intracellular Ca2+, promoting NFATc2 nuclear translocation and suppressing adipogenesis. In neuroinflammatory settings, summarized evidence links GMFB to p38 and NF-κB activation, with some ERK involvement. (xu2024glialmaturationfactorβ pages 12-13, xu2024glialmaturationfactorβ pages 11-12, xu2024glialmaturationfactorβ pages 9-11, xu2024glialmaturationfactorβ pages 7-9, amlerova2024reactivegliosisin pages 15-16)	Primary 2024 bone study combined RNA-seq/pathway analysis, immunofluorescence, nuclear-cytoplasmic protein measurements, Ca2+ assays, and cyclosporin A perturbation to connect GMFB to Ca2+-calcineurin-NFATc2; TBI review summarizes in vivo/in vitro studies showing reduced NF-κB phosphorylation and inflammatory mediators after GMFB deletion and p38/NF-κB activation after GMFB overexpression. (xu2024glialmaturationfactorβ pages 12-13, xu2024glialmaturationfactorβ pages 9-11, amlerova2024reactivegliosisin pages 15-16)	2024	Xu et al., Cell Death & Disease (2024), https://doi.org/10.1038/s41419-024-07234-z; Amlerova et al., Front Cell Neurosci (2024), https://doi.org/10.3389/fncel.2024.1335849
disease associations/biomarkers	GMFB is implicated as a disease-associated protein in osteoporosis, traumatic brain injury/neuroinflammation, diabetic retinopathy, and Alzheimer’s disease. In ADAD CSF proteomics, GMFB is reported as elevated during an early glycolytic/metabolic phase peaking around ~17 years before expected symptom onset and is annotated in module M14/category 2; in early DR review literature, elevated vitreous GMFB is linked to lysosomal dysfunction and ferroptosis in RPE cells. (xu2024glialmaturationfactorβ pages 11-12, amlerova2024reactivegliosisin pages 15-16, johnson2023cerebrospinalfluidproteomics pages 3-4, johnson2023cerebrospinalfluidproteomics pages 5-6, sun2023theidealtreatment pages 11-12)	Human/clinical evidence includes SRM-MS CSF proteomics in ADAD mutation carriers versus noncarriers (59 proteins assayed; 33 significant overall at 99% credible interval, with GMFB among early-elevated proteins) and review-cited vitreous measurements in early DR. TBI review summarizes time-course increases after injury and neuroinflammatory readouts; osteoporosis study reports increased expression in patient bone samples. (xu2024glialmaturationfactorβ pages 11-12, amlerova2024reactivegliosisin pages 15-16, johnson2023cerebrospinalfluidproteomics pages 3-4, sun2023theidealtreatment pages 11-12)	2023, 2024	Johnson et al., Nature Medicine (2023), https://doi.org/10.1038/s41591-023-02476-4; Sun et al., Front Endocrinol (2023), https://doi.org/10.3389/fendo.2023.1270145; Amlerova et al., Front Cell Neurosci (2024), https://doi.org/10.3389/fncel.2024.1335849; Xu et al., Cell Death & Disease (2024), https://doi.org/10.1038/s41419-024-07234-z
applications/therapeutic implications	Current translational use is mainly as a candidate biomarker and potential therapeutic target rather than a validated clinical target. GMFB suppression showed protective effects in OVX osteoporosis models (including shRNA/rAAV9-shRNA approaches), while preprint evidence in AD suggests GMFB is pharmacologically modulated by brain-penetrant G9a inhibition and could participate in biomarker-guided precision strategies. (xu2024glialmaturationfactorβ pages 12-13, xu2024glialmaturationfactorβ pages 11-12, chen2023novelbrainpenetrantinhibitor pages 16-18, chen2023novelbrainpenetrantinhibitor pages 11-14)	Recent primary evidence includes in vivo shGMFB/rAAV9-shRNA knockdown rescuing OVX-induced bone loss and marrow adiposity, and proteomic/phosphoproteomic preprint analyses showing AD-associated GMFB elevation in hippocampus/CSF is reduced by the G9a inhibitor MS1262. These findings support GMFB as a tractable readout/target in preclinical systems. (xu2024glialmaturationfactorβ pages 12-13, xu2024glialmaturationfactorβ pages 11-12, chen2023novelbrainpenetrantinhibitor pages 16-18, chen2023novelbrainpenetrantinhibitor pages 11-14)	2023, 2024	Xu et al., Cell Death & Disease (2024), https://doi.org/10.1038/s41419-024-07234-z; Chen et al., Research Square (2023 preprint), https://doi.org/10.21203/rs.3.rs-2743792/v1

Table: This table summarizes supported functional-annotation evidence for human GMFB/GMF-beta (UniProt P60983), emphasizing its validated identity, actin/Arp2/3 mechanism, localization, pathway links, and translational relevance. It is limited to claims directly supported by the cited evidence snippets from the specified sources.

Figure evidence (ADAD CSF cascade panel)

Cropped figure segment showing GMFB placement (module M14/category 2) and plotted statistical support in the ADAD CSF proteomic cascade. (johnson2023cerebrospinalfluidproteomics media a8d85915)

Limitations of this report (evidence availability)

The retrieved corpus contains strong support for GMFB’s Arp2/3-centered actin remodeling and multiple disease associations, but provides limited direct, primary subcellular localization statements (e.g., specific organelles/compartments) for human GMFB beyond functional inference from actin/Arp2/3 and lamellipodial roles. (shishkin2016cofilin1andother pages 22-24)
For several disease contexts (e.g., diabetic retinopathy vitreous GMFB), the evidence here comes from a reviewed mechanistic proposal without the underlying primary dataset retrieved in full; consequently, effect sizes and cohort-level statistics are not available in the provided excerpts. (sun2023theidealtreatment pages 11-12)

Key references (URLs; publication dates)

Shishkin S et al. International Journal of Molecular Sciences (2016-12). “Cofilin-1 and Other ADF/Cofilin Superfamily Members in Human Malignant Cells.” https://doi.org/10.3390/ijms18010010 (shishkin2016cofilin1andother pages 5-7)
Johnson ECB et al. Nature Medicine (2023-08). “Cerebrospinal fluid proteomics define the natural history of autosomal dominant Alzheimer’s disease.” https://doi.org/10.1038/s41591-023-02476-4 (johnson2023cerebrospinalfluidproteomics pages 3-4)
Sun W-J et al. Frontiers in Endocrinology (2023-11). “The ideal treatment timing for diabetic retinopathy…” https://doi.org/10.3389/fendo.2023.1270145 (sun2023theidealtreatment pages 11-12)
Xu J et al. Cell Death & Disease (2024-11). “Glial maturation factor-β deficiency prevents oestrogen deficiency-induced bone loss…” https://doi.org/10.1038/s41419-024-07234-z (xu2024glialmaturationfactorβ pages 1-2)
Amlerova Z et al. Frontiers in Cellular Neuroscience (2024-02). “Reactive gliosis in traumatic brain injury: a comprehensive review.” https://doi.org/10.3389/fncel.2024.1335849 (amlerova2024reactivegliosisin pages 15-16)
Chen X et al. Research Square (2023-11, preprint). “Novel brain-penetrant inhibitor of G9a methylase blocks Alzheimer’s disease proteopathology…” https://doi.org/10.21203/rs.3.rs-2743792/v1 (chen2023novelbrainpenetrantinhibitor pages 16-18)

References

(shishkin2016cofilin1andother pages 3-5): Sergey Shishkin, Lidia Eremina, Natalya Pashintseva, Leonid Kovalev, and Marina Kovaleva. Cofilin-1 and other adf/cofilin superfamily members in human malignant cells. International Journal of Molecular Sciences, 18:10, Dec 2016. URL: https://doi.org/10.3390/ijms18010010, doi:10.3390/ijms18010010. This article has 95 citations.
(xu2024glialmaturationfactorβ pages 1-2): Jun Xu, Zhongyue Huang, Si Shi, Jiangni Xia, Guangnan Chen, Kaifeng Zhou, Yiming Zhang, Chong Bian, Yuqin Shen, Xiaofan Yin, Lixia Lu, and Huijie Gu. Glial maturation factor-β deficiency prevents oestrogen deficiency-induced bone loss by remodelling the actin network to suppress adipogenesis of bone marrow mesenchymal stem cells. Cell Death & Disease, Nov 2024. URL: https://doi.org/10.1038/s41419-024-07234-z, doi:10.1038/s41419-024-07234-z. This article has 10 citations and is from a peer-reviewed journal.
(shishkin2016cofilin1andother pages 5-7): Sergey Shishkin, Lidia Eremina, Natalya Pashintseva, Leonid Kovalev, and Marina Kovaleva. Cofilin-1 and other adf/cofilin superfamily members in human malignant cells. International Journal of Molecular Sciences, 18:10, Dec 2016. URL: https://doi.org/10.3390/ijms18010010, doi:10.3390/ijms18010010. This article has 95 citations.
(shishkin2016cofilin1andother pages 22-24): Sergey Shishkin, Lidia Eremina, Natalya Pashintseva, Leonid Kovalev, and Marina Kovaleva. Cofilin-1 and other adf/cofilin superfamily members in human malignant cells. International Journal of Molecular Sciences, 18:10, Dec 2016. URL: https://doi.org/10.3390/ijms18010010, doi:10.3390/ijms18010010. This article has 95 citations.
(xu2024glialmaturationfactorβ pages 11-12): Jun Xu, Zhongyue Huang, Si Shi, Jiangni Xia, Guangnan Chen, Kaifeng Zhou, Yiming Zhang, Chong Bian, Yuqin Shen, Xiaofan Yin, Lixia Lu, and Huijie Gu. Glial maturation factor-β deficiency prevents oestrogen deficiency-induced bone loss by remodelling the actin network to suppress adipogenesis of bone marrow mesenchymal stem cells. Cell Death & Disease, Nov 2024. URL: https://doi.org/10.1038/s41419-024-07234-z, doi:10.1038/s41419-024-07234-z. This article has 10 citations and is from a peer-reviewed journal.
(shishkin2016cofilin1andother pages 7-9): Sergey Shishkin, Lidia Eremina, Natalya Pashintseva, Leonid Kovalev, and Marina Kovaleva. Cofilin-1 and other adf/cofilin superfamily members in human malignant cells. International Journal of Molecular Sciences, 18:10, Dec 2016. URL: https://doi.org/10.3390/ijms18010010, doi:10.3390/ijms18010010. This article has 95 citations.
(amlerova2024reactivegliosisin pages 15-16): Zuzana Amlerova, Martina Chmelová, M. Anděrová, and L. Vargova. Reactive gliosis in traumatic brain injury: a comprehensive review. Frontiers in Cellular Neuroscience, Feb 2024. URL: https://doi.org/10.3389/fncel.2024.1335849, doi:10.3389/fncel.2024.1335849. This article has 77 citations.
(xu2024glialmaturationfactorβ pages 7-9): Jun Xu, Zhongyue Huang, Si Shi, Jiangni Xia, Guangnan Chen, Kaifeng Zhou, Yiming Zhang, Chong Bian, Yuqin Shen, Xiaofan Yin, Lixia Lu, and Huijie Gu. Glial maturation factor-β deficiency prevents oestrogen deficiency-induced bone loss by remodelling the actin network to suppress adipogenesis of bone marrow mesenchymal stem cells. Cell Death & Disease, Nov 2024. URL: https://doi.org/10.1038/s41419-024-07234-z, doi:10.1038/s41419-024-07234-z. This article has 10 citations and is from a peer-reviewed journal.
(xu2024glialmaturationfactorβ pages 12-13): Jun Xu, Zhongyue Huang, Si Shi, Jiangni Xia, Guangnan Chen, Kaifeng Zhou, Yiming Zhang, Chong Bian, Yuqin Shen, Xiaofan Yin, Lixia Lu, and Huijie Gu. Glial maturation factor-β deficiency prevents oestrogen deficiency-induced bone loss by remodelling the actin network to suppress adipogenesis of bone marrow mesenchymal stem cells. Cell Death & Disease, Nov 2024. URL: https://doi.org/10.1038/s41419-024-07234-z, doi:10.1038/s41419-024-07234-z. This article has 10 citations and is from a peer-reviewed journal.
(xu2024glialmaturationfactorβ pages 9-11): Jun Xu, Zhongyue Huang, Si Shi, Jiangni Xia, Guangnan Chen, Kaifeng Zhou, Yiming Zhang, Chong Bian, Yuqin Shen, Xiaofan Yin, Lixia Lu, and Huijie Gu. Glial maturation factor-β deficiency prevents oestrogen deficiency-induced bone loss by remodelling the actin network to suppress adipogenesis of bone marrow mesenchymal stem cells. Cell Death & Disease, Nov 2024. URL: https://doi.org/10.1038/s41419-024-07234-z, doi:10.1038/s41419-024-07234-z. This article has 10 citations and is from a peer-reviewed journal.
(johnson2023cerebrospinalfluidproteomics pages 3-4): Erik C. B. Johnson, Shijia Bian, Rafi U. Haque, E. Kathleen Carter, Caroline M. Watson, Brian A. Gordon, Lingyan Ping, Duc M. Duong, Michael P. Epstein, Eric McDade, Nicolas R. Barthélemy, Celeste M. Karch, Chengjie Xiong, Carlos Cruchaga, Richard J. Perrin, Aliza P. Wingo, Thomas S. Wingo, Jasmeer P. Chhatwal, Gregory S. Day, James M. Noble, Sarah B. Berman, Ralph Martins, Neill R. Graff-Radford, Peter R. Schofield, Takeshi Ikeuchi, Hiroshi Mori, Johannes Levin, Martin Farlow, James J. Lah, Christian Haass, Mathias Jucker, John C. Morris, Tammie L. S. Benzinger, Blaine R. Roberts, Randall J. Bateman, Anne M. Fagan, Nicholas T. Seyfried, Allan I. Levey, Jonathan Vöglein, Ricardo Allegri, Patricio Chrem Mendez, Ezequiel Surace, Sarah B. Berman, Snezana Ikonomovic, Neelesh Nadkarni, Francisco Lopera, Laura Ramirez, David Aguillon, Yudy Leon, Claudia Ramos, Diana Alzate, Ana Baena, Natalia Londono, Sonia Moreno, Christoph Laske, Elke Kuder-Buletta, Susanne Graber-Sultan, Oliver Preische, Anna Hofmann, Kensaku Kasuga, Yoshiki Niimi, Kenji Ishii, Michio Senda, Raquel Sanchez-Valle, Pedro Rosa-Neto, Nick Fox, Dave Cash, Jae-Hong Lee, Jee Hoon Roh, Meghan Riddle, William Menard, Courtney Bodge, Mustafa Surti, Leonel Tadao Takada, V. J. Sanchez-Gonzalez, Maribel Orozco-Barajas, Alison Goate, Alan Renton, Bianca Esposito, Jacob Marsh, Carlos Cruchaga, Victoria Fernandez, Gina Jerome, Elizabeth Herries, Jorge Llibre-Guerra, William Brooks, Jacob Bechara, Jason Hassenstab, Erin Franklin, Allison Chen, Charles Chen, Shaney Flores, Nelly Friedrichsen, Nancy Hantler, Russ Hornbeck, Steve Jarman, Sarah Keefe, Deborah Koudelis, Parinaz Massoumzadeh, Austin McCullough, Nicole McKay, Joyce Nicklaus, Christine Pulizos, Qing Wang, Sheetal Mishall, Edita Sabaredzovic, Emily Deng, Madison Candela, Hunter Smith, Diana Hobbs, Jalen Scott, Peter Wang, Xiong Xu, Yan Li, Emily Gremminger, Yinjiao Ma, Ryan Bui, Ruijin Lu, Ana Luisa Sosa Ortiz, Alisha Daniels, Laura Courtney, Charlene Supnet-Bell, Jinbin Xu, and John Ringman. Cerebrospinal fluid proteomics define the natural history of autosomal dominant alzheimer’s disease. Nature Medicine, 29:1979-1988, Aug 2023. URL: https://doi.org/10.1038/s41591-023-02476-4, doi:10.1038/s41591-023-02476-4. This article has 182 citations and is from a highest quality peer-reviewed journal.
(johnson2023cerebrospinalfluidproteomics pages 5-6): Erik C. B. Johnson, Shijia Bian, Rafi U. Haque, E. Kathleen Carter, Caroline M. Watson, Brian A. Gordon, Lingyan Ping, Duc M. Duong, Michael P. Epstein, Eric McDade, Nicolas R. Barthélemy, Celeste M. Karch, Chengjie Xiong, Carlos Cruchaga, Richard J. Perrin, Aliza P. Wingo, Thomas S. Wingo, Jasmeer P. Chhatwal, Gregory S. Day, James M. Noble, Sarah B. Berman, Ralph Martins, Neill R. Graff-Radford, Peter R. Schofield, Takeshi Ikeuchi, Hiroshi Mori, Johannes Levin, Martin Farlow, James J. Lah, Christian Haass, Mathias Jucker, John C. Morris, Tammie L. S. Benzinger, Blaine R. Roberts, Randall J. Bateman, Anne M. Fagan, Nicholas T. Seyfried, Allan I. Levey, Jonathan Vöglein, Ricardo Allegri, Patricio Chrem Mendez, Ezequiel Surace, Sarah B. Berman, Snezana Ikonomovic, Neelesh Nadkarni, Francisco Lopera, Laura Ramirez, David Aguillon, Yudy Leon, Claudia Ramos, Diana Alzate, Ana Baena, Natalia Londono, Sonia Moreno, Christoph Laske, Elke Kuder-Buletta, Susanne Graber-Sultan, Oliver Preische, Anna Hofmann, Kensaku Kasuga, Yoshiki Niimi, Kenji Ishii, Michio Senda, Raquel Sanchez-Valle, Pedro Rosa-Neto, Nick Fox, Dave Cash, Jae-Hong Lee, Jee Hoon Roh, Meghan Riddle, William Menard, Courtney Bodge, Mustafa Surti, Leonel Tadao Takada, V. J. Sanchez-Gonzalez, Maribel Orozco-Barajas, Alison Goate, Alan Renton, Bianca Esposito, Jacob Marsh, Carlos Cruchaga, Victoria Fernandez, Gina Jerome, Elizabeth Herries, Jorge Llibre-Guerra, William Brooks, Jacob Bechara, Jason Hassenstab, Erin Franklin, Allison Chen, Charles Chen, Shaney Flores, Nelly Friedrichsen, Nancy Hantler, Russ Hornbeck, Steve Jarman, Sarah Keefe, Deborah Koudelis, Parinaz Massoumzadeh, Austin McCullough, Nicole McKay, Joyce Nicklaus, Christine Pulizos, Qing Wang, Sheetal Mishall, Edita Sabaredzovic, Emily Deng, Madison Candela, Hunter Smith, Diana Hobbs, Jalen Scott, Peter Wang, Xiong Xu, Yan Li, Emily Gremminger, Yinjiao Ma, Ryan Bui, Ruijin Lu, Ana Luisa Sosa Ortiz, Alisha Daniels, Laura Courtney, Charlene Supnet-Bell, Jinbin Xu, and John Ringman. Cerebrospinal fluid proteomics define the natural history of autosomal dominant alzheimer’s disease. Nature Medicine, 29:1979-1988, Aug 2023. URL: https://doi.org/10.1038/s41591-023-02476-4, doi:10.1038/s41591-023-02476-4. This article has 182 citations and is from a highest quality peer-reviewed journal.
(johnson2023cerebrospinalfluidproteomics media a8d85915): Erik C. B. Johnson, Shijia Bian, Rafi U. Haque, E. Kathleen Carter, Caroline M. Watson, Brian A. Gordon, Lingyan Ping, Duc M. Duong, Michael P. Epstein, Eric McDade, Nicolas R. Barthélemy, Celeste M. Karch, Chengjie Xiong, Carlos Cruchaga, Richard J. Perrin, Aliza P. Wingo, Thomas S. Wingo, Jasmeer P. Chhatwal, Gregory S. Day, James M. Noble, Sarah B. Berman, Ralph Martins, Neill R. Graff-Radford, Peter R. Schofield, Takeshi Ikeuchi, Hiroshi Mori, Johannes Levin, Martin Farlow, James J. Lah, Christian Haass, Mathias Jucker, John C. Morris, Tammie L. S. Benzinger, Blaine R. Roberts, Randall J. Bateman, Anne M. Fagan, Nicholas T. Seyfried, Allan I. Levey, Jonathan Vöglein, Ricardo Allegri, Patricio Chrem Mendez, Ezequiel Surace, Sarah B. Berman, Snezana Ikonomovic, Neelesh Nadkarni, Francisco Lopera, Laura Ramirez, David Aguillon, Yudy Leon, Claudia Ramos, Diana Alzate, Ana Baena, Natalia Londono, Sonia Moreno, Christoph Laske, Elke Kuder-Buletta, Susanne Graber-Sultan, Oliver Preische, Anna Hofmann, Kensaku Kasuga, Yoshiki Niimi, Kenji Ishii, Michio Senda, Raquel Sanchez-Valle, Pedro Rosa-Neto, Nick Fox, Dave Cash, Jae-Hong Lee, Jee Hoon Roh, Meghan Riddle, William Menard, Courtney Bodge, Mustafa Surti, Leonel Tadao Takada, V. J. Sanchez-Gonzalez, Maribel Orozco-Barajas, Alison Goate, Alan Renton, Bianca Esposito, Jacob Marsh, Carlos Cruchaga, Victoria Fernandez, Gina Jerome, Elizabeth Herries, Jorge Llibre-Guerra, William Brooks, Jacob Bechara, Jason Hassenstab, Erin Franklin, Allison Chen, Charles Chen, Shaney Flores, Nelly Friedrichsen, Nancy Hantler, Russ Hornbeck, Steve Jarman, Sarah Keefe, Deborah Koudelis, Parinaz Massoumzadeh, Austin McCullough, Nicole McKay, Joyce Nicklaus, Christine Pulizos, Qing Wang, Sheetal Mishall, Edita Sabaredzovic, Emily Deng, Madison Candela, Hunter Smith, Diana Hobbs, Jalen Scott, Peter Wang, Xiong Xu, Yan Li, Emily Gremminger, Yinjiao Ma, Ryan Bui, Ruijin Lu, Ana Luisa Sosa Ortiz, Alisha Daniels, Laura Courtney, Charlene Supnet-Bell, Jinbin Xu, and John Ringman. Cerebrospinal fluid proteomics define the natural history of autosomal dominant alzheimer’s disease. Nature Medicine, 29:1979-1988, Aug 2023. URL: https://doi.org/10.1038/s41591-023-02476-4, doi:10.1038/s41591-023-02476-4. This article has 182 citations and is from a highest quality peer-reviewed journal.
(sun2023theidealtreatment pages 11-12): Wen-Jie Sun, Xue-Dong An, Yue-Hong Zhang, Xue-Fei Zhao, Yu-Ting Sun, Cun-Qing Yang, Xiao-Min Kang, Lin-Lin Jiang, Hang-Yu Ji, and Feng-Mei Lian. The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern. Frontiers in Endocrinology, Nov 2023. URL: https://doi.org/10.3389/fendo.2023.1270145, doi:10.3389/fendo.2023.1270145. This article has 46 citations.
(chen2023novelbrainpenetrantinhibitor pages 16-18): Xian Chen, Ling Xie, Ryan N. Sheehy, Yan Xiong, Adil Muneer, John A. Wrobel, Kwang-Su Park, Jing Liu, J. Velez, Yanjia Luo, Yadong Li, Luis Quintanilla, Yongyi Li, Chongchong Xu, Zhexing Wen, Juan Song, Jian Jin, and Mohanish Deshmukh. Novel brain-penetrant inhibitor of g9a methylase blocks alzheimer’s disease proteopathology for precision medication. Research Square, Nov 2023. URL: https://doi.org/10.21203/rs.3.rs-2743792/v1, doi:10.21203/rs.3.rs-2743792/v1. This article has 7 citations.
(chen2023novelbrainpenetrantinhibitor pages 11-14): Xian Chen, Ling Xie, Ryan N. Sheehy, Yan Xiong, Adil Muneer, John A. Wrobel, Kwang-Su Park, Jing Liu, J. Velez, Yanjia Luo, Yadong Li, Luis Quintanilla, Yongyi Li, Chongchong Xu, Zhexing Wen, Juan Song, Jian Jin, and Mohanish Deshmukh. Novel brain-penetrant inhibitor of g9a methylase blocks alzheimer’s disease proteopathology for precision medication. Research Square, Nov 2023. URL: https://doi.org/10.21203/rs.3.rs-2743792/v1, doi:10.21203/rs.3.rs-2743792/v1. This article has 7 citations.
(shishkin2016cofilin1andother pages 1-3): Sergey Shishkin, Lidia Eremina, Natalya Pashintseva, Leonid Kovalev, and Marina Kovaleva. Cofilin-1 and other adf/cofilin superfamily members in human malignant cells. International Journal of Molecular Sciences, 18:10, Dec 2016. URL: https://doi.org/10.3390/ijms18010010, doi:10.3390/ijms18010010. This article has 95 citations.

Citations

amlerova2024reactivegliosisin pages 15-16
johnson2023cerebrospinalfluidproteomics pages 3-4
sun2023theidealtreatment pages 11-12
chen2023novelbrainpenetrantinhibitor pages 16-18
johnson2023cerebrospinalfluidproteomics pages 5-6
chen2023novelbrainpenetrantinhibitor pages 11-14
https://doi.org/10.3390/ijms18010010;
https://doi.org/10.1038/s41419-024-07234-z
https://doi.org/10.1038/s41419-024-07234-z;
https://doi.org/10.3389/fncel.2024.1335849
https://doi.org/10.1038/s41591-023-02476-4;
https://doi.org/10.3389/fendo.2023.1270145;
https://doi.org/10.3389/fncel.2024.1335849;
https://doi.org/10.21203/rs.3.rs-2743792/v1
https://doi.org/10.3390/ijms18010010
https://doi.org/10.1038/s41591-023-02476-4
https://doi.org/10.3389/fendo.2023.1270145
https://doi.org/10.3390/ijms18010010,
https://doi.org/10.1038/s41419-024-07234-z,
https://doi.org/10.3389/fncel.2024.1335849,
https://doi.org/10.1038/s41591-023-02476-4,
https://doi.org/10.3389/fendo.2023.1270145,
https://doi.org/10.21203/rs.3.rs-2743792/v1,

📄 View Raw YAML

id: P60983
gene_symbol: GMFB
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  GMFB encodes glia maturation factor beta, a small ADF-H/cofilin-superfamily
  GMF protein whose best-supported conserved molecular role is Arp2/3-dependent
  branched actin network remodeling. Current evidence supports Arp2/3 complex
  binding, inhibition of Arp2/3-mediated actin nucleation, and actin filament
  debranching, with cell-context effects on lamellipodial dynamics, neural/glial
  phenotypes, inflammation, and Ca2+-calcineurin-NFAT signaling.
existing_annotations:
  - term:
      id: GO:0071933
      label: Arp2/3 complex binding
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        Arp2/3 complex binding is the most specific molecular-function
        annotation for GMFB's conserved GMF-family activity.
      action: ACCEPT
      reason: >-
        Falcon research supports GMFB as an Arp2/3-centered actin-network
        remodeling factor rather than a generic actin-binding or growth-factor
        protein.
      supported_by:
        - reference_id: file:human/GMFB/GMFB-deep-research-falcon.md
          supporting_text: >-
            Current consensus from the cited review and recent primary work is
            that GMF-beta is an actin-network remodeling factor that binds the
            Arp2/3 complex
  - term:
      id: GO:0030864
      label: cortical actin cytoskeleton
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        Cortical/leading-edge branched actin structures are an appropriate
        active site for GMFB-mediated actin network remodeling.
      action: ACCEPT
      reason: >-
        The location is supported by the biology of Arp2/3-branched actin
        networks even though the direct microscopy evidence in the falcon report
        is mostly from cell-context studies.
      supported_by:
        - reference_id: file:human/GMFB/GMFB-deep-research-falcon.md
          supporting_text: >-
            its described mechanism--binding Arp2/3, regulating
            lamellipodial/leading-edge dynamics--places its primary functional
            locus at cytoskeletal actin networks enriched for Arp2/3-dependent
            branching
  - term:
      id: GO:0071846
      label: actin filament debranching
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        Actin filament debranching is a specific and conserved GMF-family
        biological process.
      action: ACCEPT
      reason: >-
        This annotation captures GMFB's direct contribution to turnover of
        Arp2/3-branched actin arrays.
      supported_by:
        - reference_id: file:human/GMFB/GMFB-deep-research-falcon.md
          supporting_text: >-
            stimulates debranching of branched actin filament networks
  - term:
      id: GO:0034316
      label: negative regulation of Arp2/3 complex-mediated actin nucleation
    evidence_type: IBA
    original_reference_id: GO_REF:0000033
    review:
      summary: >-
        GMFB negatively regulates Arp2/3-mediated nucleation as part of its
        branched-actin remodeling mechanism.
      action: ACCEPT
      reason: >-
        This term is mechanistically specific and complements the debranching
        annotation.
      supported_by:
        - reference_id: file:human/GMFB/GMFB-deep-research-falcon.md
          supporting_text: >-
            inhibits Arp2/3-driven actin nucleation/branch formation
  - term:
      id: GO:0007165
      label: signal transduction
    evidence_type: IEA
    original_reference_id: GO_REF:0000108
    review:
      summary: >-
        GMFB can influence signaling pathways downstream of actin remodeling, but
        the broad signal-transduction annotation is indirect and likely derived
        from legacy growth-factor/activity links.
      action: MARK_AS_OVER_ANNOTATED
      reason: >-
        The current core function is Arp2/3-branched actin remodeling; signaling
        effects such as Ca2+-NFAT or inflammatory pathway changes are downstream
        cellular outcomes rather than a primary GO process for GMFB.
      supported_by:
        - reference_id: file:human/GMFB/GMFB-deep-research-falcon.md
          supporting_text: >-
            the most direct mechanistic chain supported in the evidence is GMFB
            to actin remodeling to Ca2+ to calcineurin to NFATc2
  - term:
      id: GO:0003779
      label: actin binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: >-
        The ADF-H domain places GMFB in actin-network biology, but the more
        precise molecular-function annotation is Arp2/3 complex binding.
      action: MODIFY
      reason: >-
        Falcon research explicitly notes that GMFB does not primarily bind actin
        directly and instead acts through Arp2/3.
      proposed_replacement_terms:
        - id: GO:0071933
          label: Arp2/3 complex binding
      supported_by:
        - reference_id: file:human/GMFB/GMFB-deep-research-falcon.md
          supporting_text: >-
            unlike canonical ADF/cofilins--does not primarily bind actin
            directly, and instead acts mainly through the Arp2/3 complex
  - term:
      id: GO:0008083
      label: growth factor activity
    evidence_type: IEA
    original_reference_id: GO_REF:0000043
    review:
      summary: >-
        The growth factor activity annotation reflects the historical protein
        name and early biological activity assays rather than a current
        mechanistic molecular function.
      action: REMOVE
      reason: >-
        There is no strong evidence here that GMFB is a secreted growth factor in
        the GO molecular-function sense; its supported core role is intracellular
        Arp2/3/actin network remodeling.
      supported_by:
        - reference_id: file:human/GMFB/GMFB-uniprot.txt
          supporting_text: Belongs to the actin-binding proteins ADF family. GMF subfamily.
  - term:
      id: GO:0071846
      label: actin filament debranching
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: >-
        The InterPro2GO debranching annotation agrees with the IBA annotation and
        the falcon-summarized GMF-family mechanism.
      action: ACCEPT
      reason: >-
        Actin filament debranching is a specific, supported biological process
        for GMFB.
      supported_by:
        - reference_id: file:human/GMFB/GMFB-deep-research-falcon.md
          supporting_text: >-
            GMF-beta controls branched actin content and lamellipodial dynamics
            in fibroblasts
  - term:
      id: GO:0071933
      label: Arp2/3 complex binding
    evidence_type: IEA
    original_reference_id: GO_REF:0000002
    review:
      summary: >-
        The InterPro2GO Arp2/3 binding annotation is consistent with stronger IBA
        evidence and current GMFB literature.
      action: ACCEPT
      reason: >-
        This is the most informative molecular-function term in the GMFB GOA
        file.
      supported_by:
        - reference_id: file:human/GMFB/GMFB-deep-research-falcon.md
          supporting_text: >-
            Foundational primary work cited in the review describes GMF as a
            cofilin homolog that binds Arp2/3
  - term:
      id: GO:0004860
      label: protein kinase inhibitor activity
    evidence_type: TAS
    original_reference_id: PMID:8639570
    review:
      summary: >-
        The cited in vitro study supports phosphorylated GMF inhibiting ERK1/2,
        but the broad kinase inhibitor term should be replaced with the more
        specific serine/threonine kinase inhibitor activity term.
      action: MODIFY
      reason: >-
        ERK1/2 are protein serine/threonine kinases, so the specific replacement
        term preserves the direct in vitro observation without elevating this
        historical MAPK effect above GMFB's current core Arp2/3-dependent actin
        remodeling function.
      proposed_replacement_terms:
        - id: GO:0030291
          label: protein serine/threonine kinase inhibitor activity
      supported_by:
        - reference_id: PMID:8639570
          supporting_text: >-
            recombinant glia maturation factor (GMF), a 17-kDa brain protein,
            inhibits the activity of mitogen-activated protein (MAP) kinase in
            the test tube assay
  - term:
      id: GO:0006468
      label: protein phosphorylation
    evidence_type: TAS
    original_reference_id: PMID:7598724
    review:
      summary: >-
        This is a substrate/process misannotation: the cited paper describes GMF
        being phosphorylated by kinases, not GMFB catalyzing protein
        phosphorylation.
      action: REMOVE
      reason: >-
        GMFB is not a kinase; phosphorylation of GMFB is a post-translational
        modification of GMFB, not a biological process carried out by GMFB.
      supported_by:
        - reference_id: PMID:7598724
          supporting_text: >-
            recombinant glia maturation factor (GMF), a 17-kD brain protein, can
            be phosphorylated in vitro at the serine residue by protein kinase C
            (PKC), protein kinase A (PKA), and casein kinase II (CKII)
  - term:
      id: GO:0007399
      label: nervous system development
    evidence_type: TAS
    original_reference_id: PMID:1712830
    review:
      summary: >-
        Early GMFB work supports biological activity in neural/glial contexts,
        but nervous system development is broad relative to the current
        mechanistic understanding.
      action: KEEP_AS_NON_CORE
      reason: >-
        Retain as a historical non-core process association, while core function
        should focus on Arp2/3/actin remodeling.
      supported_by:
        - reference_id: PMID:1712830
          supporting_text: >-
            Glia maturation factor-beta, a protein found in the brains of all
            vertebrates thus far examined, appears to play a role in the
            differentiation, maintenance, and regeneration of the nervous system.
  - term:
      id: GO:0008047
      label: enzyme activator activity
    evidence_type: TAS
    original_reference_id: PMID:8798479
    review:
      summary: >-
        The cited in vitro study supports phosphorylated GMF enhancing p38 MAP
        kinase activity, but the broad enzyme activator term should be replaced
        with the specific protein serine/threonine kinase activator term.
      action: MODIFY
      reason: >-
        p38 MAP kinase is a protein serine/threonine kinase, so the specific
        replacement term captures the direct in vitro result while leaving
        Arp2/3-dependent actin remodeling as the core function.
      proposed_replacement_terms:
        - id: GO:0043539
          label: protein serine/threonine kinase activator activity
      supported_by:
        - reference_id: PMID:8798479
          supporting_text: >-
            PKA-phosphorylated GMF strongly enhances the activity of a related
            but distinct subfamily of MAP kinase, the p38 MAP kinase
references:
  - id: GO_REF:0000002
    title: Gene Ontology annotation through association of InterPro records with GO terms
    findings: []
  - id: GO_REF:0000033
    title: Annotation inferences using phylogenetic trees
    findings: []
  - id: GO_REF:0000043
    title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword mapping
    findings: []
  - id: GO_REF:0000108
    title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links
    findings: []
  - id: PMID:1712830
    title: Molecular cloning and expression of biologically active human glia maturation factor-beta.
    findings:
      - statement: Early cloning work associated GMFB with neural differentiation and maintenance.
        supporting_text: >-
          Glia maturation factor-beta, a protein found in the brains of all
          vertebrates thus far examined, appears to play a role in the
          differentiation, maintenance, and regeneration of the nervous system.
  - id: PMID:7598724
    title: Phorbol ester stimulates rapid intracellular phosphorylation of glia maturation factor.
    findings:
      - statement: GMFB is phosphorylated by kinases and is not itself a kinase.
        supporting_text: >-
          recombinant glia maturation factor (GMF), a 17-kD brain protein, can be
          phosphorylated in vitro at the serine residue by protein kinase C
          (PKC), protein kinase A (PKA), and casein kinase II (CKII)
  - id: PMID:8639570
    title: In vitro inhibition of MAP kinase (ERK1/ERK2) activity by phosphorylated glia maturation factor (GMF).
    findings:
      - statement: Phosphorylated GMF inhibited ERK1/2 activity in vitro.
        supporting_text: >-
          recombinant glia maturation factor (GMF), a 17-kDa brain protein,
          inhibits the activity of mitogen-activated protein (MAP) kinase in the
          test tube assay
  - id: PMID:8798479
    title: In vitro enhancement of p38 mitogen-activated protein kinase activity by phosphorylated glia maturation factor.
    findings:
      - statement: Phosphorylated GMF enhanced p38 MAP kinase activity in vitro.
        supporting_text: >-
          PKA-phosphorylated GMF strongly enhances the activity of a related but
          distinct subfamily of MAP kinase, the p38 MAP kinase
  - id: file:human/GMFB/GMFB-uniprot.txt
    title: UniProt text export for GMFB (P60983)
    findings:
      - statement: UniProt places GMFB in the GMF subfamily of ADF-family actin-binding proteins.
        supporting_text: Belongs to the actin-binding proteins ADF family. GMF subfamily.
  - id: file:human/GMFB/GMFB-deep-research-falcon.md
    title: Falcon deep research report for GMFB
    findings:
      - statement: Falcon research supports GMFB as an Arp2/3-centered actin network remodeling factor.
        supporting_text: >-
          Current consensus from the cited review and recent primary work is
          that GMF-beta is an actin-network remodeling factor that binds the
          Arp2/3 complex
core_functions:
  - description: >-
      Arp2/3 complex binding and remodeling of branched actin networks by
      promoting actin filament debranching and inhibiting Arp2/3-mediated actin
      nucleation.
    molecular_function:
      id: GO:0071933
      label: Arp2/3 complex binding
    directly_involved_in:
      - id: GO:0071846
        label: actin filament debranching
      - id: GO:0034316
        label: negative regulation of Arp2/3 complex-mediated actin nucleation
    locations:
      - id: GO:0030864
        label: cortical actin cytoskeleton
    supported_by:
      - reference_id: file:human/GMFB/GMFB-deep-research-falcon.md
        supporting_text: >-
          GMF-beta controls branched actin content and lamellipodial dynamics in
          fibroblasts
proposed_new_terms: []
suggested_questions:
  - question: Which human cell types require GMFB's direct Arp2/3 debranching activity rather than downstream effects of altered actin-state signaling?
  - question: Are the historical ERK inhibition and p38 activation observations physiologically relevant for endogenous GMFB, or in vitro effects of phosphorylated recombinant protein?
  - question: What specific cortical actin structures recruit GMFB in neurons, glia, and mesenchymal stem cells?
suggested_experiments:
  - description: Purified human GMFB Arp2/3 binding, nucleation-inhibition, and debranching assays using TIRF microscopy with phosphomimetic and nonphosphorylatable GMFB variants.
    experiment_type: biochemical reconstitution
    hypothesis: GMFB directly binds Arp2/3 and remodels branched actin independently of MAPK-modulator activity.
  - description: Endogenous GMFB tagging in astrocytes, neurons, and mesenchymal stem cells followed by live imaging of Arp2/3, F-actin, and GMFB during protrusion and recovery from actin depolymerization.
    experiment_type: live-cell imaging/genome editing
    hypothesis: GMFB localizes to dynamic cortical Arp2/3-branched actin structures in the cell types where disease-associated phenotypes are reported.
  - description: Knock-in separation-of-function mutations that preserve GMFB expression but disrupt Arp2/3 binding, followed by NFAT, p38, and inflammatory readouts.
    experiment_type: genome editing/signaling assay
    hypothesis: GMFB-linked signaling phenotypes are downstream of its Arp2/3/actin-remodeling function.

Gene Description

Existing Annotations Review

Core Functions

Arp2/3 complex binding and remodeling of branched actin networks by promoting actin filament debranching and inhibiting Arp2/3-mediated actin nucleation.