NEW YORK (AP) Maria Sharapova's undefeated record in three-set matches ended Friday, and so did her stay at the U.S. Open.

No. 26 seed Flavia Pennetta of Italy knocked off the 2006 champion 6-3, 3-6, 6-4 in the third round to hand Sharapova her first loss in 13 three-setters this year.

I didn't know that,'' Pennetta said when asked if she was aware of Sharapova's perfect record in matches that went the distance.It was a good thing.''

Sharapova made 12 double-faults, including two in the last game. She did not look sharp over a 2 hour, 29-minute match that featured plenty of nervous tennis. Sharapova made 60 unforced errors and lost four break points while trailing 2-0 in the third set.

``I didn't feel comfortable with most of my game today,'' Sharapova said.

Pennetta, who also had a big win in Arthur Ashe Stadium two years ago against Vera Zvonareva that put her in the quarterfinals, said calming her nerves was the key as the match wore on.

I was just trying to be focused on my game, trying not to think about the score,'' she said.But when you're there, too many things come into your mind. You just try to focus and play your best tennis.''

The loss by third-seeded Sharapova, the runner-up at Wimbledon this year, kicked yet another top player out of a wide-open draw. Already, the defending Wimbledon and French Open champions have been dispatched and two-time defending U.S. Open champion Kim Clijsters didn't enter because of an injury.

Earlier, No. 2 Vera Zvonareva defeated No. 30 Anabel Medina Garrigues and No. 1 Caroline Wozniacki is still in the draw, but neither has won a Grand Slam title. Sharapova was largely considered the biggest remaining threat to No. 28 Serena Williams, but now the Russian is gone, as well.

It's disappointing to lose in the middle of nowhere, disappointing to lose in New York,'' Sharapova said.Losing isn't fun for anyone because we work to win. We don't work to lose.''

Elsewhere at Flushing Meadows, No. 28 John Isner defeated fellow American Robby Ginepri 6-4, 6-3, 6-4 to get to the third round. Isner, who won the title in Winston-Salem last week, is on a seven-match winning streak and said his confidence is ``high as it's ever been.''

``I feel like I'm moving very well, I'm getting to balls and able to get a lot more balls back in play because I'm very comfortable out there,'' Isner said.

Another all-American matchup between No. 21 Andy Roddick and 18-year-old Jack Sock was the main event scheduled at night in Ashe Stadium. Before that, 19-year-old American Christina McHale was to play No. 25 Maria Kirilenko of Russia.

Other winners included 2009 champion, No. 18 Juan Martin del Potro and No. 24 seed Juan Ignacio Chela. On the women's side, No. 13 Peng Shuai of China defeated No. 19 Julia Goerges of Germany, 6-4, 7-6 (1).