Protein Family Models

Date:

2024-08-14

This model represents the IIIC subfamily of the Haloacid Dehalogenase (HAD) superfamily of aspartate nucleophile hydrolases. Subfamily III (also including IIIA - TIGR01662 and IIIB - PF03767) contains sequences which do not contain either of the insert domains (between the 1st and 2nd conserved catalytic motifs, subfamily I - TIGR01493, TIGR01509, TIGR01549, TIGR01488, TIGR01494, TIGR01658, TIGR01544 and TIGR01545, or between the 2nd and 3rd, subfamily II - TIGR01460 and TIGR01484). Subfamily IIIC contains five relatively distantly related clades: a family of viral proteins (TIGR01684), a family of eukaryotic proteins called MDP-1 and a family of archaeal proteins most closely related to MDP-1 (TIGR01685), a family of bacteria including the Streptomyces FkbH protein (TIGR01686), and a small clade including the Pasteurella BcbF and EcbF proteins. The overall lack of species overlap among these clades may indicate a conserved function, but the degree of divergence between the clades and the differences in archetecture outside of the domain in some clades warns against such a conclusion. No member of this subfamily is characterized with respect to function, however the MDP-1 protein [1] is a characterized phosphatase. All of the characterized enzymes within subfamily III are phosphatases, and all of the active site residues characteristic of HAD-superfamily phosphatases [2] are present in subfamily IIIC.

Date:

2019-09-10

This model describes a domain of a family of proteins of unknown overall function. One of these, however, is a modular polyketide synthase 4800 amino acids in length from Streptomyces avermilitis in which this domain is the C-terminal segment. By contrast, the FkbH protein from Streptomyces hygroscopicus aparently contains only this domain. The remaining members of the family all contain an additional N-terminal domain of between 200 and 275 amino acids which show less than 20% identity to one another. It seems likely then that these proteins are involved in disparate functions, probably the biosynthesis of different natural products. For instance, the FkbH gene is found in a gene cluster believed to be responsible for the biosynthesis of unususal "PKS extender units" in the ascomycin pathway [2]. This domain is composed of two parts, the first of which is a member of subfamily IIIC (TIGR01681) of the haloacid dehalogenase (HAD) superfamily of aspartate-nucleophile hydrolases. All of the characterized enzymes within subfamily III are phosphatases, and all of the active site residues characteristic of HAD-superfamily phosphatases [1] are present in this domain. The C-terminal portion of this domain is unique to this family (by BLAST).

Date:

2019-09-10

haloacid dehalogenase (HAD)-IIIC family phosphatase from the FkbH subfamily may be involved in methoxymalonyl-ACP biosynthesis; the HAD family includes phosphoesterases, ATPases, phosphonatases, dehalogenases, and sugar phosphomutases acting on a remarkably diverse set of substrates

Date:

2024-05-17