Mufti Nizamuddin Shamzai, who had called for a "Jihad," or holy war, against the United States after the invasions of Afghanistan and Iraq, was fatally wounded, police said. His son, another relative, a bodyguard and a driver were also hit.

It was not immediately clear who was behind the attack or whether it was a sectarian killing.

"As soon as we sat in the car, we heard gun shots and we immediately ducked," the cleric's relative, Rafiuddin, told reporters. "I felt a strong pain in my leg, I had been shot and than I saw Mufti Shamzai Sahib covered in blood."

Religious Affairs Minister Ijazul Haq told Pakistan television that the shooting was a condemnable act of terrorism.

"This is purely a terrorist act by those who want anarchy and chaos and who want to create sectarian tensions," he said.

Provincial security adviser Aftab Sheikh told Reuters that it had been known Shamzai's life was under threat and the government had provided him with armed bodyguards.

"It was a targeted killing and according to our information about 10 to 12 people were involved," he said. "It is a continuation of recent acts of violence and terrorism."

The crackle of gunfire was heard after violent demonstrations broke out in several parts of Karachi. Small groups of Shamzai's followers came out on the streets, pelting vehicles with stones and burning tires.

A Reuters correspondent at the scene said thousands of people, many carrying batons, had gathered near Shamzai's Islamic school, located in a central commercial area, and had set fire to two banks, several shops and a petrol station.

"There is a lot of smoke in the air from the burning tires and building, glass is scattered all around from damaged vehicles, and people are really charged," he said.

"There is heavy shelling of tear gas and police fired gun shots in the air to disperse the crowd," another witness said.