Human and zebrafish hydroxysteroid dehydrogenase like 1 (HSDL1) proteins are inactive enzymes but conserved among species.
Hydroxysteroid dehydrogenase like 1 protein (HSDL1) is an uncharacterized member of short-chain dehydrogenase/reductase (SDR) protein family. In search for functional assignment of both human and zebrafish HSDL1 we characterized the subcellular localization as well as the tissue distribution and performed a screen for putative substrates of HSDL1 enzymes. Surprisingly, human HSDL1 shows exchange of an amino acid in the active center (Sx(12)FSxxK instead of Sx(12)YSxxK) that is considered critical for catalysis. Native human HSDL1 expressed in cells did not show enzymatic activity with any of the substrates tested. Expression of the point mutation F218Y HSDL1 though, resulted in the detection of weak dehydrogenase activity towards steroid and retinoid substrates. The role of this inactivating mutation is uncertain but was found to be conserved in many other vertebrate species, including zebrafish. Identification of protein interaction partners by yeast two-hybrid system suggests that despite the potential lack of enzymatic activity HSDL1 might retain regulatory functions in the cell.
Meier
Marc
M
Helmholtz Zentrum München, German Research Center for Environmental Health, Institute of Experimental Genetics, Genome Analysis Center, Neuherberg, Germany.
Tokarz
Janina
J
Haller
Ferdinand
F
Mindnich
Rebekka
R
Adamski
Jerzy
J
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D020134:Catalytic Domain; D017124:Conserved Sequence; D017931:DNA Primers; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010802:Phylogeny; D011485:Protein Binding; D014176:Protein Biosynthesis; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D013379:Substrate Specificity; D020798:Two-Hybrid System Techniques
D017931:DNA Primers; C464422:HSDL1 protein, human; D006913:Hydroxysteroid Dehydrogenases