Article · Wikipedia archive · Last revised Jun 19, 2026

NHL repeat

The NHL repeat, named after ncl-1, HT2A and lin-41, is an amino acid sequence found largely 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-terminus alpha-amidation of biological peptides. In many it occurs in tandem arrays, for example in the RING finger beta-box, coiled-coil (RBCC) eukaryotic growth regulators. The arthropod 'Brain Tumor' protein is one such growth regulator that contains a 6-bladed NHL-repeat beta-propeller.

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Jun 19, 2026
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NHL repeat
Structure of the brain tumor-Pumilio translation repressor complex.1
Identifiers
SymbolNHL
PfamPF01436
Pfam clanCL0186
InterProIPR001258
SCOP21q7f / SCOPe / SUPFAM
CDDcd05819
Available protein structures:
PDB  1q7f​ , 1rwi​ , 1rwl​ IPR001258 PF01436 (ECOD; PDBsum)  
AlphaFold

The NHL repeat, named after ncl-1, HT2A and lin-41, is an amino acid sequence found largely 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-terminus alpha-amidation of biological peptides.2 In many it occurs in tandem arrays, for example in the RING finger beta-box, coiled-coil (RBCC) eukaryotic growth regulators.3 The arthropod 'Brain Tumor' protein (Brat; Q8MQJ9) is one such growth regulator that contains a 6-bladed NHL-repeat beta-propeller.14

The NHL repeats are also found in serine/threonine protein kinase (STPK) in 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.

The NHL repeat has also been used to design a family of fully symmetrical 6-blade beta-propeller proteins called "Pizza".5 These proteins can also be engineered to bind mineral nanocrystals.6

References

References

  1. Edwards TA, Wilkinson BD, Wharton RP, Aggarwal AK (October 2003). "Model of the brain tumor-Pumilio translation repressor complex". Genes Dev. 17 (20): 2508–2513. doi:10.1101/gad.1119403. PMC 218144. PMID 14561773.
  2. Kano S, Miyajima N, Fukuda S, Hatakeyama S (July 2008). "Tripartite motif protein 32 facilitates cell growth and migration via degradation of Abl-interactor 2". Cancer Res. 68 (14): 5572–5580. doi:10.1158/0008-5472.CAN-07-6231. PMID 18632609.
  3. Slack FJ, Ruvkun G (December 1998). "A novel repeat domain that is often associated with RING finger and B-box motifs". Trends Biochem. Sci. 23 (12): 474–5. doi:10.1016/S0968-0004(98)01299-7. PMID 9868369.
  4. Edwards TA, Pyle SE, Wharton RP, Aggarwal AK (April 2001). "Structure of Pumilio reveals similarity between RNA and peptide binding motifs". Cell. 105 (2): 281–9. doi:10.1016/S0092-8674(01)00318-X. PMID 11336677. S2CID 9341061.
  5. Tame, Jeremy R. H.; Zhang, Kam Y. J.; Park, Sam-Yong; Unzai, Satoru; Terada, Daiki; Simoncini, David; Addy, Christine; Noguchi, Hiroki; Voet, Arnout R. D. (21 October 2014). "Computational design of a self-assembling symmetrical β-propeller protein". Proceedings of the National Academy of Sciences. 111 (42): 15102–15107. Bibcode:2014PNAS..11115102V. doi:10.1073/pnas.1412768111. ISSN 0027-8424. PMC 4210308. PMID 25288768.
  6. Voet, AR; Noguchi, H; Addy, C; Zhang, KY; Tame, JR (17 August 2015). "Biomineralization of a Cadmium Chloride Nanocrystal by a Designed Symmetrical Protein". Angewandte Chemie International Edition. 54 (34): 9857–60. doi:10.1002/anie.201503575. PMID 26136355.
This article incorporates text from the public domain Pfam and InterPro: IPR001258