Dubai: Set a Test record 491 to win after Pakistan declared on 354-6, the tourists reached 130-3 by the close of day four in Dubai on Sunday.
England face a fight to avoid defeat on the final day of the second Test after Pakistan continued their dominance.
Joe Root (59) and Jonny Bairstow (six) were at the crease with England needing another 361 runs to win or bat out the final day on a weary Dubai stadium pitch on Monday.
Pakistan declared their second innings at 354-6 after Younis Khan notched 118 for his 31st century.
Earlier, Younus Khan went to 118 - his 31st Test century - and Asad Shafiq made 79 as Pakistan added 132 to their overnight total.
England will retain some hope of saving the game while the accomplished Root remains at the crease.
However, with leg-spinner Yasir Shah and slow left-armer Zulfiqar Babar finding increasing turn on a wearing pitch, Pakistan will reasonably expect to wrap up victory and take a 1-0 lead in the three-match series.
Earlier Pakistan added 132 runs before declaring 35 minutes after lunch, with Younis in top form.
Younis punched paceman Stuart Broad to the point boundary for his 11th four to reach three figures off 193 balls, his third hundred against England.
He was finally dismissed as he tried to pace the run-rate, skying a catch off leg-spinner Adil Rasheed. In all he hit 13 boundaries during his 354-minute knock.
Pakistan, resuming on 222-3, looked for quick runs.
Misbah had scored a brilliant 102 in Pakistan's first innings of 378, but failed to add to his overnight 87.
He played an uppish shot to a slower delivery from fast bowler James Anderson which landed in the safe hands of Cook at mid-off.
Misbah hit eight boundaries and five sixes in his enterprising 147-ball innings.
England's bowlers toiled hard to check the flow of runs as leg-spinner Adil Rasheed conceded 107 runs before finally getting a wicket.
Ali trapped Shafiq leg-before wicket to finish with 1-60. Shafiq hit eight boundaries in his 112-ball knock. He added 113 runs for the fifth wicket with Younis.
Skipper Misbah-ul-Haq declared the innings at the fall of Shafiq's wicket.
Anderson with 2-22 and Mark Wood 2-44 were the most successful bowlers.
Brief scores
Pakistan - 378 (Misbah 102, Wood 3-39, Moeen 3-108) and 354/6d (Younis 118, Misbah 87, Shafiq 79)
England - 242 (Root 88, Cook 65, Riaz 4-66, Shah 4-93) and 130/3 (Root 59*)
Status - England need 361 runs to win