I have updated my main DPM server to Update Rollup 5 for System Center 2012 R2 Data Protection Manager and all went well.

All Protected servers updated and rebooted and continued protection - EXCEPT one;

Physical Windows Server 2012 R2 Datacenter.

Tried Manual install - no luck

Removed Protection Agent / rebooted / re-installed - no luck

Installed all updates / re-install - no luck

this seems to be the only indicated problem in MSDPMAgentInstall.LOG.....

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Property(S): PATCHMediaSrcProp = C:\Windows\Microsoft Data Protection Manager\DPM\ProtectionAgents\RA\4.2.1292.0\DPMProtectionAgent_KB3021791.msp
MSI (s) (04:34) [09:24:23:772]: Product: Microsoft System Center 2012 R2 DPM Protection Agent - Update 'Microsoft System Center 2012 R2 DPM Protection Agent Update - KB3021791' could not be installed. Error code 1603. Additional information is available in the log file C:\Windows\\Temp\MSDPMAgentInstall.LOG.

MSI (s) (04:34) [09:24:23:772]: Windows Installer installed an update. Product Name: Microsoft System Center 2012 R2 DPM Protection Agent. Product Version: 4.2.1292.0. Product Language: 1033. Manufacturer: Microsoft Corporation. Update Name: Microsoft System Center 2012 R2 DPM Protection Agent Update - KB3021791. Installation success or error status: 1603.

MSI (s) (04:34) [09:24:23:772]: Note: 1: 1729
MSI (s) (04:34) [09:24:23:772]: Note: 1: 2205 2:  3: Error
MSI (s) (04:34) [09:24:23:772]: Note: 1: 2228 2:  3: Error 4: SELECT `Message` FROM `Error` WHERE `Error` = 1729
MSI (s) (04:34) [09:24:23:772]: Note: 1: 2205 2:  3: Error
MSI (s) (04:34) [09:24:23:772]: Note: 1: 2228 2:  3: Error 4: SELECT `Message` FROM `Error` WHERE `Error` = 1709
MSI (s) (04:34) [09:24:23:772]: Product: Microsoft System Center 2012 R2 DPM Protection Agent -- Configuration failed.

MSI (s) (04:34) [09:24:23:772]: Windows Installer reconfigured the product. Product Name: Microsoft System Center 2012 R2 DPM Protection Agent. Product Version: 4.2.1292.0. Product Language: 1033. Manufacturer: Microsoft Corporation. Reconfiguration success or error status: 1603.

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Any help would be greatly appreciated.

Hotfix for known issue with Update Rollup 5 for System Center 2012 R2 Data Protection Manager
http://www.microsoft.com/en-us/download/details.aspx?id=45914&WT.mc_id=rss_alldownloads_all