Serine/threonine-protein kinase MRCK beta (CDC42BPB)
The protein contains 1711 amino acids for an estimated molecular weight of 194315 Da.
Serine/threonine-protein kinase which is an important downstream effector of CDC42 and plays a role in the regulation of cytoskeleton reorganization and cell migration. Regulates actin cytoskeletal reorganization via phosphorylation of PPP1R12C and MYL9/MLC2 (PubMed:21457715, PubMed:21949762). In concert with MYO18A and LURAP1, is involved in modulating lamellar actomyosin retrograde flow that is crucial to cell protrusion and migration (PubMed:18854160). Phosphorylates PPP1R12A (PubMed:21457715). In concert with FAM89B/LRAP25 mediates the targeting of LIMK1 to the lamellipodium resulting in its activation and subsequent phosphorylation of CFL1 which is important for lamellipodial F-actin regulation (By similarity). (updated: Sept. 12, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt.
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Biological Process
Actin cytoskeleton reorganization
Actomyosin structure organization
Cell migration
Cytoskeleton organization
Establishment or maintenance of cell polarity
Intracellular signal transduction
Peptidyl-threonine phosphorylation
Protein phosphorylation
Signal transduction
The reference OMIM entry for this protein is 614062
Cdc42-binding protein kinase, beta; cdc42bpb
Cdc42bp-beta
Myotonic dystrophy kinase-related cdc42-binding kinase, beta; mrckb
Mrck-beta
CLONING
Using CDC42 (116952) as bait in an expression screen of a human brain cDNA library, Leung et al. (1998) obtained a partial cDNA for CDC42BPB, which they designated MRCK-beta. They obtained full-length cDNAs encoding Mrck-beta and a related protein, Mrck-alpha (CDC42BPA; 603412), from a rat cDNA library. The deduced rat Mrck-alpha and Mrck-beta proteins contain 1,732 and 1,702 amino acids, respectively. Both have an N-terminal kinase domain, followed by a central coiled-coil region, a cysteine-rich region, a pleckstrin (PLEK; 173570) homology (PH) domain, and a C-terminal p21 GTPase (see HRAS; 190020)-binding domain. Northern blot analysis detected Mrck-beta expression in all rat tissues examined, with highest expression in kidney and lung. Expression of MRCK-alpha and MRCK-beta was also detected in HeLa cells. By RT-PCR walking, Moncrieff et al. (1999) cloned full-length human CDC42BPB from human fetal brain mRNA. The deduced protein contains 1,711 amino acids. It shares 90% amino acid identity and conservation of domain structure with rat Cdc42bpb. Northern blot analysis detected a major 7-kb transcript in all human tissues examined, with highest expression in heart, brain, and placenta.GENE FUNCTION
Ng et al. (2004) showed that the isolated kinase inhibitory motif of MRCK-gamma (CDC42BPG; 613991) bound the kinase domains of MRCK-alpha and MRCK-beta and inhibited their catalytic activities. By immunoprecipitation analysis, Tan et al. (2008) found that Lrap35a (LURAP1; 616129) interacted with Mrck-alpha and Mrck-beta and with the cytoskeletal myosin Myo18a (610067) in rat brain extracts. A similar complex of MRCK, LRAP35A, and MYO18A was identified in human cell lines. Knockdown and overexpression studies revealed that the MRCK complex was responsible for assembly of lamellar actomyosin bundles and a subnuclear actomyosin network. LRAP35A functioned as an adaptor protein that bound independently to MYO18A and MRCK. Binding of LRAP35A to the kinase inhibitory motif of MRCK activated MRCK for phosphorylation of MYO18A. The MRCK complex moved in concert with the retrograde flow of actomyosin bundles and was required for cell protrusion and migration. Using yeast 2-hybrid analysis, Huo et al. (2011) found that MRCK-beta bound to the C-terminal ZU5 domain of ZO1 (TJP1; 601009). The interaction likely caused a conformational change in the ZU5 domain. Cotransfection of MRCK-beta and ZO1 led to prominent colocalization of the 2 proteins at the leading edge of COS-7 cells. Mutation analysis showed that the ZU5 domain of ZO1 was required for targeting of MRCK-beta to the leading edge. Formation of the ZO1-MRCK-beta complex required priming of MRCK-beta by CDC42. Disruption of the ZO1/MRCK-beta complex inhibited MRCK-beta-mediated cell migration.MAPPING
By radiation hybrid analysis and FISH, Moncrieff et al. (1999) mapped the CDC42BPB gene to chromosome 14q32.3. ... More on the omim web site
Dec. 10, 2018: Protein entry updated
Automatic update: model status changed
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 614062 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).