On modern large-portrait bills, the second letter of the serial number indicates the issuing Federal Reserve District. E.g. AB12345678C would indicate a bill printed for the New York district ("B")
Current $1 and $2 bills and all older bills had only a single leading letter which designated the district. In addition the district was identified by a special seal showing the district letter, and each corner of the bill had the district's corresponding number.
The issuing bank identifying letter and number is printed on the obverse of all US $1 banknotes. A1 indicates that the note was issued by the Boston Federal Reserve Bank.
All U.S. dollar bills have a letter A through L to indicate a Federal Reserve Bank branch where the bill was first issued. K refers to the Federal Reserve Bank of Dallas.
$5 Federal Reserve Notes have been issued for over a century. Please check your bill again and post a new, separate question with its date and what letter if any is next to the date.
The small letter+number on the bottom-left corner of any Federal Reserve note indicates which of the 12 banks issued it - in the case of 'B' and the number '2', this means the note was issued in New York.
If you mean the letter inside the round seal, it's an indicator of which of the 12 Federal Reserve districts issued the bill. If you're referring to another letter, please post a more specific question.
Modern ones are only worth face value, but $5 Federal Reserve Notes have been issued for nearly a century. If your bill is older than the 1970s please post a new, separate question with its date and what letter, if any, is next to the date.
Until recent redesigns of currency US bills that were "Federal Reserve Notes" (almost all bills printed) had a single large letter between A and L, which identified one of the twelve regional branches of the Federal Reserve Bank. (for example, notes with the letter "D" were issued from the Federal Reserve Bank in Cleveland, OH) New designs for most US bills omit these letters. They remain only on one-dollar bills.
The reason a red seal $5 bill doesn't have a Federal Reserve letter on it is because the red seal version is NOT a Federal Reserve note. Red seal bills are United States notes.
$20 Federal Reserve Notes have been issued for over a century so more information is needed. Please post a new, separate question with the bill's date and what letter, if any, is next to the date. You don't need to include the serial number, though.
The Federal Reserve Bank of Minneapolis
The letter 'I' on a Federal Reserve Note indicates that the note was printed in Minneapolis.
"A" is the highest series letter for 1928 $50 Federal Reserve Notes. "K" is most likely the Federal Reserve District letter. The series letter, if any, on US bills is next to the date. Please see the question "What is the value of a 1928 US 50 dollar Federal Reserve Note?" for more information on values.