RACGAP1

Last updated
RACGAP1
Protein RACGAP1 PDB 2ovj.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases RACGAP1 , CYK4, HsCYK-4, ID-GAP, MgcRacGAP, Rac GTPase activating protein 1, CDAN3B
External IDs OMIM: 604980 MGI: 1349423 HomoloGene: 8077 GeneCards: RACGAP1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_001253808
NM_001253809
NM_012025

RefSeq (protein)

NP_001240737
NP_001240738
NP_036155

Location (UCSC) Chr 12: 49.98 – 50.03 Mb Chr 15: 99.52 – 99.55 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Rac GTPase-activating protein 1 is an enzyme that in humans is encoded by the RACGAP1 gene. [5]

Function

Rho GTPases control a variety of cellular processes. There are 3 subtypes of Rho GTPases in the Ras superfamily of small G proteins: RHO (see MIM 165370), RAC (see RAC1; MIM 602048), and CDC42 (MIM 116952). GTPase-activating proteins (GAPs) bind activated forms of Rho GTPases and stimulate GTP hydrolysis. Through this catalytic function, Rho GAPs negatively regulate Rho-mediated signals. GAPs may also serve as effector molecules and play a role in signaling downstream of Rho and other Ras-like GTPases.[supplied by OMIM]. [6] Over-expression of RACGAP1 is observed in multiple human cancers including breast cancer, [7] gastric cancer [8] and colorectal cancer. [9] Evidence show that RACGAP1 can modulate mitochondrial quality control by stimulating mitopahy and mitochondrial biogenesis in breast cancer. [10] [11] Knocking out RACGAP1 in vitro using CRISPR/Cas9 leads to cytokinesis failure. [12]

Interactions

RACGAP1 has been shown to interact with ECT2, [13] Rnd2 [14] and SLC26A8. [15]

During cytokinesis, RACGAP1 has been shown to interact with KIF23 to form the centralspindlin complex. [16] This complex is essential for the formation of the central spindle. RACGAP1 also interacts with PRC1 to stabilize and maintain the central spindle as anaphase proceeds. [17] RACGAP1 can also interact with ECT2 during anaphase of cytokinesis, loss of RACGAP1 leads to cytokinesis failure. [18]

Related Research Articles

<span class="mw-page-title-main">CDC42</span> Protein-coding gene in the species Homo sapiens

Cell division control protein 42 homolog is a protein that in humans is encoded by the CDC42 gene. Cdc42 is involved in regulation of the cell cycle. It was originally identified in S. cerevisiae (yeast) as a mediator of cell division, and is now known to influence a variety of signaling events and cellular processes in a variety of organisms from yeast to mammals.

<span class="mw-page-title-main">RAC1</span> Protein-coding gene in humans

Rac1, also known as Ras-related C3 botulinum toxin substrate 1, is a protein found in human cells. It is encoded by the RAC1 gene. This gene can produce a variety of alternatively spliced versions of the Rac1 protein, which appear to carry out different functions.

<span class="mw-page-title-main">Transforming protein RhoA</span> Protein and coding gene in humans

Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.

<span class="mw-page-title-main">ROCK1</span> Protein

ROCK1 is a protein serine/threonine kinase also known as rho-associated, coiled-coil-containing protein kinase 1. Other common names are ROKβ and P160ROCK. ROCK1 is a major downstream effector of the small GTPase RhoA and is a regulator of the actomyosin cytoskeleton which promotes contractile force generation. ROCK1 plays a role in cancer and in particular cell motility, metastasis, and angiogenesis.

<span class="mw-page-title-main">T-cell lymphoma invasion and metastasis-inducing protein 1</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor TIAM1 is a protein that in humans is encoded by the TIAM1 gene.

<span class="mw-page-title-main">RAC3</span> Mammalian protein found in Homo sapiens

Ras-related C3 botulinum toxin substrate 3 (Rac3) is a G protein that in humans is encoded by the RAC3 gene. It is an important component of intracellular signalling pathways. Rac3 is a member of the Rac subfamily of the Rho family of small G proteins. Members of this superfamily appear to regulate a diverse array of cellular events, including the control of cell growth, cytoskeletal reorganization, and the activation of protein kinases.

<span class="mw-page-title-main">RALA</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Ral-A (RalA) is a protein that in humans is encoded by the RALA gene on chromosome 7. This protein is one of two paralogs of the Ral protein, the other being RalB, and part of the Ras GTPase family. RalA functions as a molecular switch to activate a number of biological processes, majorly cell division and transport, via signaling pathways. Its biological role thus implicates it in many cancers.

<span class="mw-page-title-main">RhoC</span> Protein-coding gene in the species Homo sapiens

RhoC is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC.

<span class="mw-page-title-main">ECT2</span> Gene of the species Homo sapiens

Protein ECT2 is a protein that in humans is encoded by the ECT2 gene.

<span class="mw-page-title-main">DLC1</span> Protein-coding gene in the species Homo sapiens

Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene.

<span class="mw-page-title-main">Chimerin 2</span> Protein-coding gene in the species Homo sapiens

Chimerin 2 (beta-chimaerin) is a protein that in humans is encoded by the CHN2 gene.

<span class="mw-page-title-main">RhoG</span> Protein-coding gene in the species Homo sapiens

RhoG is a small monomeric GTP-binding protein, and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RHOG.

<span class="mw-page-title-main">Citron kinase</span> Enzyme found in humans

Citron Rho-interacting kinase is an enzyme that in humans is encoded by the CIT gene.

<span class="mw-page-title-main">ANLN</span> Mammalian protein found in Homo sapiens

Anillin is a conserved protein implicated in cytoskeletal dynamics during cellularization and cytokinesis. The ANLN gene in humans and the scraps gene in Drosophila encode Anillin. In 1989, anillin was first isolated in embryos of Drosophila melanogaster. It was identified as an F-actin binding protein. Six years later, the anillin gene was cloned from cDNA originating from a Drosophila ovary. Staining with anti-anillin antibody showed the anillin localizes to the nucleus during interphase and to the contractile ring during cytokinesis. These observations agree with further research that found anillin in high concentrations near the cleavage furrow coinciding with RhoA, a key regulator of contractile ring formation.

<span class="mw-page-title-main">RALB</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Ral-B (RalB) is a protein that in humans is encoded by the RALB gene on chromosome 2. This protein is one of two paralogs of the Ral protein, the other being RalA, and part of the Ras GTPase family. RalA functions as a molecular switch to activate a number of biological processes, majorly cell division and transport, via signaling pathways. Its biological role thus implicates it in many cancers.

<span class="mw-page-title-main">Rnd2</span> Protein-coding gene in the species Homo sapiens

Rnd2 is a small signaling G protein, and is a member of the Rnd subgroup of the Rho family of GTPases. It is encoded by the gene RND2.

<span class="mw-page-title-main">VAV3</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide exchange factor VAV3 is a protein that in humans is encoded by the VAV3 gene.

Chimerin is a type of nerve tissue protein.

<span class="mw-page-title-main">ARHGAP31</span> Protein-coding gene in the species Homo sapiens

The Rho GTPase activating protein 31 is encoded in humans by the ARHGAP31 gene. It is a Cdc42/Rac1 GTPase regulator.

Centralspindlin is a motor complex implicated in cell division. It contributes to virtually every step in cytokinesis, It is highly conserved in animal cells as a component of the spindle midzone and midbody. Centralspindlin is required for the assembly of the mitotic spindle as well as for microtubule bundling and anchoring of midbody microtubules to the plasma membrane. This complex is also implicated in tethering the spindle apparatus to the plasma membrane during cytokinesis This interaction permits cleavage furrow ingression. In addition, centralspindlin's interaction with the ESCRT III allows for abscission to occur.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000161800 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000023015 - Ensembl, May 2017
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  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
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  9. Imaoka H, Toiyama Y, Saigusa S, et al. (March 2015). "RacGAP1 expression, increasing tumor malignant potential, as a predictive biomarker for lymph node metastasis and poor prognosis in colorectal cancer". Carcinogenesis. 36 (3): 346–54. doi: 10.1093/carcin/bgu327 . PMID   25568185.
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  14. Naud N, Touré A, Liu J, et al. (May 2003). "Rho family GTPase Rnd2 interacts and co-localizes with MgcRacGAP in male germ cells". The Biochemical Journal. 372 (Pt 1): 105–112. doi:10.1042/BJ20021652. PMC   1223378 . PMID   12590651.
  15. Toure A, Morin L, Pineau C, et al. (June 2001). "Tat1, a novel sulfate transporter specifically expressed in human male germ cells and potentially linked to rhogtpase signaling". The Journal of Biological Chemistry. 276 (23): 20309–20315. doi: 10.1074/jbc.M011740200 . PMID   11278976.
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Further reading