Yes, you can do that and you would need to define the domain and SIP proxy under Configuration > Outbound calls section from the CMS Web Admin. This would be similar to the following snippet from my lab.
I would recommend going through the deployment guide to understand the dial-plan and S4B integration better in particular. If there are users on VCS/CUCM making calls to skype, inbound call rules need to be added as well and any transformations etc. Similarly, Skype clients calling into CMS, you would again need inbound calls rules. CMS only cares about the domain portion. If the incoming domain does not match an incoming rule and does not match a forwarding rule, the call will be rejected.
