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We derive the explicit Hamiltonian of twisted bilayer graphene (TBG) with Coulomb interaction projected into the flat bands, and study the symmetries of the Hamiltonian. First, we show that all projected TBG Hamiltonians can be written as Positive Semidefinite Hamiltonian, the first example of which was found in [PRL 122, 246401]. We then prove that the interacting TBG Hamiltonian exhibits an exact U(4) symmetry in the exactly flat band (nonchiral-flat) limit. We further define, besides a first chiral limit where the AA stacking hopping is zero, a new second chiral limit where the AB/BA stacking hopping is zero. In the first chiral-flat limit (or second chiral-flat limit) with exactly flat bands, the TBG is enhanced to have an exact U(4)$\times$U(4) symmetry, whose generators are different between the two chiral limits. While in the first chiral limit and in the non-chiral case these symmetries have been found in [PRX 10, 031034] for the $8$ lowest bands, we here prove that they are valid for projection into any $8 n_\text{max}$ particle-hole symmetric TBG bands, with $n_\text{max}>1$ being the practical case for small twist angles $<1^\circ$. Furthermore, in the first or second chiral-nonflat limit without flat bands, an exact U(4) symmetry still remains. We also elucidate the link between the U(4) symmetry presented here and the similar but different U(4) of [PRL 122, 246401]. Furthermore, we show that our projected Hamiltonian can be viewed as the normal-ordered Coulomb interaction plus a Hartree-Fock term from passive bands, and exhibits a many-body particle-hole symmetry which renders the physics symmetric around charge neutrality. We also provide an efficient parameterization of the interacting Hamiltonian. The existence of two chiral limits, with an enlarged symmetry suggests a possible duality of the model yet undiscovered.