ABR, RhoGEF and GTPase activating protein

ABR
Identifiers
AliasesABR, MDB, active BCR-related, RhoGEF and GTPase activating protein, ABR activator of RhoGEF and GTPase
External IDsOMIM: 600365; MGI: 107771; GeneCards: ABR
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

29

109934

Ensembl

ENSG00000159842
ENSG00000278741
ENSG00000276016

ENSMUSG00000017631

UniProt

Q12979

Q5SSL4

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 17: 1 – 1.23 MbChr 11: 76.31 – 76.51 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Active breakpoint cluster region-related protein is a protein that in humans is encoded by the ABR gene.[5]

Gene

The ABR activator of RhoGEF and GTPase, also symbolized as ABR, gene has a reported 13 alternatively spliced transcript variants.[6] This gene is found to have ubiquitous expression within 23 human tissues, including the heart and brain.[7] The protein encoded by ABR shares homology with the Breakpoint Cluster Region (BCR) gene located on chromosome 22 and has shown to share similar protein functions.[8]

Function

The protein encoded by this gene contains a GTPase-activating protein domain, a domain found in members of the Rho family of GTP-binding protein. They are selective for Rac.[9] Despite their "GTPase-activating" domain they actually reduce the activity of Rac.[8] They keep mature innate immune system cells from becoming overactive.[9]

The ABR is an inhibitor of ras-related C3 botulinum toxin substrate 1 (RAC1), a protein found to influence cell growth, motility of the cell, and maintain adhesion to neighboring epithelial cells.[10] Recent papers suggest ABR has tumor suppressor properties in leukemia because of its role as a RAC1 inhibitor and is being researched as a potential therapy treatment in leukemia patients.[11] Other studies suggest ABR plays an important role in vestibular morphogenesis.[12]

Knockout phenotype

Double-knockout of ABR and BCR in vitro causes macrophage overactivation.[8] Double-knockout of ABR and BCR in mice lead to dysfunctional astroglia and abnormal postnatal development of the cerebellum.[13]

Single ABR and single BCR knockout mice are each more sensitive to intraperitoneal LPS than normal mice and recover more slowly.[9] Double knockout mice failed to make any recovery and all died within 2 days.[9]

References

  1. 1 2 3 ENSG00000278741, ENSG00000276016 GRCh38: Ensembl release 89: ENSG00000159842, ENSG00000278741, ENSG00000276016 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000017631 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ "Entrez Gene: ABR, RhoGEF and GTPase activating protein". Retrieved 2018-05-23.
  6. ↑ "Gene: Abr (ENSMUSG00000017631) - Summary - Mus musculus - Ensembl genome browser 89". may2017.archive.ensembl.org. Retrieved 2022-05-03.
  7. ↑ "ABR ABR activator of RhoGEF and GTPase [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-05-03.
  8. 1 2 3 Cho YJ, Cunnick JM, Yi SJ, Kaartinen V, Groffen J, Heisterkamp N (February 2007). "Abr and Bcr, two homologous Rac GTPase-activating proteins, control multiple cellular functions of murine macrophages". Molecular and Cellular Biology. 27 (3): 899–911. doi:10.1128/MCB.00756-06. PMC 1800684. PMID 17116687.
  9. 1 2 3 4 Cunnick JM, Schmidhuber S, Chen G, Yu M, Yi SJ, Cho YJ, et al. (November 2009). "Bcr and Abr cooperate in negatively regulating acute inflammatory responses". Molecular and Cellular Biology. 29 (21): 5742–5750. doi:10.1128/MCB.00357-09. PMC 2772743. PMID 19703997.
  10. ↑ "ABR Gene - GeneCards | ABR Protein | ABR Antibody". www.genecards.org. Retrieved 2022-05-17.
  11. ↑ Namasu CY, Katzerke C, Bräuer-Hartmann D, Wurm AA, Gerloff D, Hartmann JU, et al. (November 2017). "ABR, a novel inducer of transcription factor C/EBPα, contributes to myeloid differentiation and is a favorable prognostic factor in acute myeloid leukemia". Oncotarget. 8 (61): 103626–103639. doi:10.18632/oncotarget.22093. PMC 5732755. PMID 29262589.
  12. ↑ Kaartinen V, Nagy A, Gonzalez-Gomez I, Groffen J, Heisterkamp N (April 2002). "Vestibular dysgenesis in mice lacking Abr and Bcr Cdc42/RacGAPs". Developmental Dynamics. 223 (4): 517–525. doi:10.1002/dvdy.10071. PMID 11921339. S2CID 29212113.
  13. ↑ Kaartinen V, Gonzalez-Gomez I, Voncken JW, Haataja L, Faure E, Nagy A, et al. (November 2001). "Abnormal function of astroglia lacking Abr and Bcr RacGAPs". Development. 128 (21). Cambridge, England: 4217–4227. doi:10.1242/dev.128.21.4217. PMID 11684658.

Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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