NHL repeat
IPR001258
Definition
The NHL repeat, named after NCL-1, HT2A and Lin-41, is a conserved structural motif present in a large number of eukaryotic and prokaryotic proteins. For example, the repeat is found in a variety of enzymes of the copper type II, ascorbate-dependent monooxygenase family, which catalyse the C-terminal alpha-amidation of biological peptides PMID:1894599 and in a large family of growth regulators. Many NHL-containing proteins have additional domains such as a RING finger, a B-box zinc finger or a coiled-coil motif. In many, it occurs in tandem arrays, for example in the ring finger β-box, coiled-coil (RBCC) eukaryotic growth regulators PMID:9868369 or the 'Brain Tumor' protein (Brat) [[cite:PMID:14561773], [cite:PMID:11336677]]. The NHL repeats are also found in serine/threonine protein kinase (STPK) in a diverse range of pathogenic bacteria. These STPK are transmembrane receptors with an intracellular N-terminal kinase domain and extracellular C-terminal sensor domain. In the STPK PknD from Mycobacterium tuberculosis, the sensor domain forms a rigid, six-bladed b-propeller composed of NHL repeats with a flexible tether to the transmembrane domain PMID:15136047. The NHL domain is a six-bladed β-propeller, with the blades arrayed in a radial fashion around a central axis, and each blade composed of a highly twisted four-stranded antiparallel β-sheet PMID:14561773. The innermost strand of each blade is labelled 'a' and the outermost strand, 'd'. Like in other β-propellers, the sequence repeats are offset with respect to the blades of the propeller, such that any given 40-residue NHL repeat spans strands 'b-d' of one propeller blade and strand 'a' of the subsequent blade. This offset ensures circularisation of the propeller because the last strand of the final sequence repeat acts as an innermost strand of the blade that harbours strands 'b-d' from the first sequence repeat. According to structural model analysis, the NHL domain could be involved in protein-protein interaction PMID:14561773.
9 human proteins with this domain
Each is a reviewed human protein in the Seroatlas serome and a potential autoantibody target; this domain groups them into one antibody-relevant category. Every entry links to its own record.
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