Myosin phosphatase Rho-interacting protein (MPRIP)
The protein contains 1025 amino acids for an estimated molecular weight of 116533 Da.
Targets myosin phosphatase to the actin cytoskeleton. Required for the regulation of the actin cytoskeleton by RhoA and ROCK1. Depletion leads to an increased number of stress fibers in smooth muscle cells through stabilization of actin fibers by phosphorylated myosin. Overexpression of MRIP as well as its F-actin-binding region leads to disassembly of stress fibers in neuronal cells. (updated: Oct. 10, 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.
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| Variant | Description |
|---|---|
| dbSNP:rs3744137 |
The reference OMIM entry for this protein is 612935
Myosin phosphatase rho-interacting protein; mprip
Mrip
Kiaa0864
P116 rho-interacting protein; p116rip
Rip3
CLONING
By yeast 2-hybrid analysis of a mouse brain cDNA library to isolate RhoA (165390)-binding proteins, Gebbink et al. (1997) cloned mouse Mprip, which they called p116Rip. The deduced 1,024-amino acid protein has a calculated molecular mass of 116.4 kD. It has 2 proline-rich sequences near the N-terminus that are predicted to bind SH3 domains, a central pleckstrin homology (PH) domain, and a C-terminal coiled-coil region, which overlaps with the RhoA-binding domain. Northern blot analysis detected p116Rip in all mouse tissues examined. By sequencing clones obtained from a size-fractionated human brain cDNA library, Nagase et al. (1998) cloned MPRIP, which they designated KIAA0864. The deduced protein contains 1,218 amino acids. RT-PCR ELISA detected highest MPRIP expression in ovary, followed by heart, brain, liver, kidney, lung, skeletal muscle, and testis with lower expression in pancreas and spleen. Using the myosin-binding subunit of myosin phosphatase (MBS, or PPP1R12A; 602021) as bait in a yeast 2-hybrid screen of a human aorta cDNA library, Surks et al. (2003) cloned MPRIP, which they called MRIP. The deduced 1,024-amino acid protein shares 90% identity with mouse and rat p116Rip3. It has 2 PH domains flanking 2 polyproline motifs in the N-terminal half, and 3 coiled-coil domains in the C-terminal half. It also has sites for myristoylation and phosphorylation, and it has a putative nuclear localization signal. Immunohistochemical analysis of coronary artery smooth muscle cells showed that MRIP colocalized with MBS and RhoA at actin stress fibers. MRIP did not show nuclear localization. Western blot analysis detected endogenous MRIP at an apparent molecular mass of 125 kD in human smooth muscle cell lines.GENE FUNCTION
Gebbink et al. (1997) showed that mouse p116Rip interacted with both the GDP- and GTP-bound forms of RhoA in a mouse neuroblastoma cell line. Overexpression of p116Rip stimulated cell flattening and neurite outgrowth in a way similar to dominant-negative RhoA. Cells that overexpressed p116Rip failed to retract neurites in response to lysophosphatidic acid. Gebbink et al. (1997) concluded that p116RIP counters RhoA signaling in neurite outgrowth. Mulder et al. (2003) found that, rather than directly binding to RhoA, mouse p116Rip interacted with filamentous F-actin (see 102610) via its N-terminal region. In mouse and monkey cell lines, p116Rip colocalized with dynamic F-actin structures such as stress fibers, cortical microfilaments, filopodia, and lamellipodia ruffles. p116Rip induced F-actin bundling in vitro via its actin-binding domain. However, overexpression of p116Rip or its N-terminal actin-binding domain in cell culture disrupted the actin cytoskeleton and interfered with growth factor-induced contractility and lamellipodia formation. Using coimmunoprecipitation analysis, Surks et al. (2003) confirmed that human MRIP interacted with MBS in vascular smooth muscle cells. Mutation analysis showed that the second coiled-coil domain of MRIP interacted with the leucine zipper domain of MBS. MRIP also bound both GDP- and GTP-RhoA following expression in COS-1 cells, and MBS was not required for this interaction. MRIP immunoprecipitation also led to recovery of PP1 (PPA1; 179030) and cGMP-dependent protein kinase (PRKG1; 176894), and interacted with these proteins indirectly via its interaction with MBS. Using gene silencing with human vascular smooth muscle cells, Surks et al. (2005) sho ... More on the omim web site
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 612935 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).