Details for: ABRA

Gene ID: 137735

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: ABRA

Ensembl ID: ENSG00000174429

Description: actin binding Rho activating protein

Selected Context(s):  Overall

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • regular atrial cardiac myocyte CL0002129
    CSI 2.17
    rCSI 7%
    PRS 99.98
  • regular ventricular cardiac myocyte CL0002131
    CSI 1.05
    rCSI 6.55%
    PRS 99.83

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

Explore relationships of the current gene. Select an Interaction Source: 'ONTOLOGY' for shared pathways (GO/Reactome) or 'STRING' for protein-protein interactions. Further refine by selecting context genes and comparing Cell Significance Index (CSI) scores between baseline and target cell types and their specific contexts.

Comma-separated if multiple.
Comma-separated if multiple.
Legend:
  • Query Gene
  • Node Color (Target Cell CSI, relative to current network):
    • Very High
    • High
    • Medium
    • Low
    • Very Low
    • CSI N/A
  • Node Size: Proportional to Target Cell CSI magnitude
  • STRING PPI Edge
  • Shared Pathway Edge (ONTOLOGY)

Loading network (please wait)...

Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Actin Binding Rho Activating Protein ([ABRA](/details-gene/137735)) is a protein-coding gene located on chromosome 8q23.1. As its name suggests, [ABRA](/details-gene/137735) functions as a crucial molecular link between the actin cytoskeleton and intracellular signaling cascades. It is primarily involved in [actin cytoskeleton organization](/details-go/GO:0030036) and the [positive regulation of rho protein signal transduction](/details-go/GO:0035025). **Overall**, expression data reveals that [ABRA](/details-gene/137735) is a highly specific marker for cardiac muscle cells, with its most significant expression found in [regular atrial cardiac myocyte](/details-cell/CL0002129) and [regular ventricular cardiac myocyte](/details-cell/CL0002131). This restricted expression pattern, combined with its function, points to a specialized role in regulating the structure and signaling responses of the heart muscle, particularly in the context of striated muscle function and gene transcription ([Link](https://doi.org/10.1074/jbc.m202216200)). ## Cellular Roles and Expression Landscape **Overall**, the expression profile of [ABRA](/details-gene/137735) demonstrates remarkable specificity for the heart. Analysis across diverse human cell types shows that its significance is almost exclusively confined to cardiac myocytes. - **Primary Expression Context:** The gene is most significant in [regular atrial cardiac myocyte](/details-cell/CL0002129) (CSI: 2.17) and [regular ventricular cardiac myocyte](/details-cell/CL0002131) (CSI: 1.05). This high CSI in both major types of heart muscle cells underscores its fundamental role in cardiac biology. This highly focused expression pattern suggests that [ABRA](/details-gene/137735) is not a general-purpose cytoskeletal regulator but rather a specialized component of the cardiac muscle machinery. Its function is likely tailored to the unique physiological demands of cardiomyocytes, such as contraction-relaxation cycles and responses to hemodynamic stress. The lack of significant expression in other lineages implies a minimal role in non-muscle cell types. ## Pathways and Molecular Function The functional annotations for [ABRA](/details-gene/137735) are highly consistent with its specific expression in cardiac muscle. It localizes to the [actin cytoskeleton](/details-go/GO:0015629) and the [sarcomere](/details-go/GO:0030017), the fundamental contractile unit of striated muscle cells. - **Cytoskeletal Interaction:** Through its [actin binding](/details-go/GO:0003779) capacity, [ABRA](/details-gene/137735) directly engages with the core structural components of the myocyte, contributing to [actin cytoskeleton organization](/details-go/GO:0030036). - **Signal Transduction:** A key function of [ABRA](/details-gene/137735) is the [positive regulation of rho protein signal transduction](/details-go/GO:0035025). Rho signaling is a master regulator of cell shape, adhesion, and migration, and in the heart, it is a critical pathway in the response to mechanical stress and the development of cardiac hypertrophy. - **Gene Regulation:** [ABRA](/details-gene/137735) connects these cytoskeletal and signaling roles to gene expression by participating in the [positive regulation of transcription by rna polymerase ii](/details-go/GO:0045944). Research has shown it acts as a striated muscle activator of serum response factor (SRF)-dependent transcription, providing a direct mechanism for translating cytoskeletal cues into changes in the cellular transcriptome ([Link](https://doi.org/10.1074/jbc.m202216200)). ## Research Directions The specific role of [ABRA](/details-gene/137735) as a muscle-specific signaling hub makes it an important subject for cardiovascular research, particularly in the context of heart disease. **Proposed Hypotheses:** 1. Given its function as a positive regulator of Rho signaling, a key pathway in pathological cardiac growth, it is hypothesized that overexpression or hyperactivation of [ABRA](/details-gene/137735) is a contributing factor to the development of maladaptive cardiac hypertrophy in response to pressure overload. 2. [ABRA](/details-gene/137735) may function as a mechanosensor at the sarcomere, translating mechanical forces generated during the cardiac cycle into RhoA activation and subsequent SRF-mediated gene expression, thereby playing a critical role in the physiological adaptation of the heart. **Experimental Approach:** To test the hypothesis that [ABRA](/details-gene/137735) acts as a cardiac mechanosensor, one could utilize an in vitro model system. - **Methodology:** Human iPSC-derived cardiomyocytes could be cultured on flexible silicone membranes. A CRISPR-Cas9 system would be used to generate [ABRA](/details-gene/137735) knockout (KO) cell lines. Both wild-type and KO cardiomyocytes would be subjected to cyclical mechanical stretch to mimic increased cardiac load. - **Analysis:** The primary readouts would be the activation of the RhoA pathway (measured by RhoA-GTP pull-down assays) and the expression of downstream SRF target genes (e.g., *ACTA1*, *MYH7*) assessed by RT-qPCR and RNA-sequencing. A significantly blunted RhoA and SRF response to mechanical stretch in the [ABRA](/details-gene/137735) KO cells compared to controls would provide strong evidence for its role as a key mechanotransducer. **Therapeutic Potential:** The high cardiac specificity of [ABRA](/details-gene/137735) makes it an attractive therapeutic target. In pathological conditions like cardiac hypertrophy and heart failure, where RhoA signaling is often chronically elevated, [ABRA](/details-gene/137735) would be a candidate for **inhibition**. Developing a small molecule or peptide-based inhibitor to disrupt the interaction of [ABRA](/details-gene/137735) with RhoA or its upstream activators could potentially mitigate pathological cardiac remodeling with fewer systemic side effects than a broad inhibitor of the Rho pathway.

Genular Protein ID: 1555262801

Symbol: ABRA_HUMAN

Name: Actin-binding Rho-activating protein

UniProtKB Accession Codes:

Q8N0Z2

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 5 Ensembl 1 GO 9 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 RNAct 1 RefSeq 1 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 neXtProt 1

Citations:

PubMed ID: 11983702

Title: STARS, a striated muscle activator of Rho signaling and serum response factor-dependent transcription.

PubMed ID: 11983702

DOI: 10.1074/jbc.m202216200

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 17974005

Title: The full-ORF clone resource of the German cDNA consortium.

PubMed ID: 17974005

DOI: 10.1186/1471-2164-8-399

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

Sequence Information:

  • Length: 381
  • Mass: 43117
  • Checksum: AC5B8D4D9A267C46
  • Sequence:
    • MAPGEKESGE GPAKSALRKI RTATLVISLA RGWQQWANEN SIRQAQEPTG WLPGGTQDSP 
QAPKPITPPT SHQKAQSAPK SPPRLPEGHG DGQSSEKAPE VSHIKKKEVS KTVVSKTYER 
GGDVSHLSHR YERDAGVLEP GQPENDIDRI LHSHGSPTRR RKCANLVSEL TKGWRVMEQE 
EPTWRSDSVD TEDSGYGGEA EERPEQDGVQ VAVVRIKRPL PSQVNRFTEK LNCKAQQKYS 
PVGNLKGRWQ QWADEHIQSQ KLNPFSEEFD YELAMSTRLH KGDEGYGRPK EGTKTAERAK 
RAEEHIYREM MDMCFIICTM ARHRRDGKIQ VTFGDLFDRY VRISDKVVGI LMRARKHGLV 
DFEGEMLWQG RDDHVVITLL K