The 31-year-old has long been on the periphery at the Irish province but injuries to Ireland second-row Tuohy and Iain Henderson will see him take centre stage in the GUINNESS PRO12 over the coming weeks.
He will make his first start of the season against Zebre and is one of ten changes to the team that beat Cardiff Blues last weekend.
Craig Gilroy returns at full-back - with Tommy Bowe and Michael Allen flanking him on the wings - while starlet Stuart McCloskey lines up alongside Darren Cave at inside centre.
Callum Black, Rob Herring and Declan Fitzpatrick all come into the front-row as Ulster look to remain unbeaten against an Italian outfit since October 2011.
And one player who won't be lacking any motivation is McComb, as he aims to become a cornerstone of his province's GUINNESS PRO12 challenge this year.
"Obviously for Dan it is disappointing," said McComb. "For me, I have to look at it as an opportunity. I need to put my hand up and say pick me. I am here to play rugby and I want to be playing week in, week out.
"Zebre are a very physical side, especially at home. They have passion and pride and we know it is going to be a tough game.
"Games against them in the past have been very close. We know that we have to play for the full 80 and take it to them.
"We know that they are going to be physical so we just need to do the small things right, be competitive in the first 20 minutes and go from there."
Zebre have received a boost on the injury front with the return of Italy flyer Leonardo Sarto - and will need his input as they aim to buck of a run of four straight PRO12 defeats.
One of those losses came against Ulster, who scored five tries in a 33-13 victory, in round two.
Important to Ulster's strong start has been Franco van der Merwe, a summer arrival from Super Rugby's Lions, and McComb can't wait to pack down with him once more.
"He is great," added McComb. "Last weekend (against Cardiff) was the first time playing alongside him.
"It's nice to have a fresh face in there. He has been calling the line-outs and is like Johann (Muller) in the leadership that he brings."
At Stadio XXV Aprile, 4pm local time (3pm Ireland & UK). Live on BBC NI
Referee: Peter Fitzgibbon (IRFU, 59th competition game)
Assistant Referees: Mateo Liperini, Stefano Penne (both IRFU)
Citing Commissioner: Russell Howell (WRU)
TMO: Carlo Damasco (FIR)
Guinness PRO12
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