WD repeat-containing proteins

Home
Targets
Other protein targets
WD repeat-containing proteins

Unless otherwise stated all data on this page refer to the human proteins. Gene information is provided for human (Hs), mouse (Mm) and rat (Rn).

Overview

Show »« Hide

Members of the WD repeat-containing protein family are involved in many cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation.

Targets

3305

NACHT and WD repeat domain containing 1 Show summary »« Hide summary

Target Id	3305
Nomenclature	NACHT and WD repeat domain containing 1
Genes	NWD1 (Hs), Nwd1 (Mm), Nwd1 (Rn)
Ensembl ID	ENSG00000188039 (Hs), ENSMUSG00000048148 (Mm), ENSRNOG00000048622 (Rn)
UniProtKB AC	Q149M9 (Hs), A6H603 (Mm)
Comment	Nwd1 is a member of the signal transduction ATPases with numerous domains (STAND) protein superfamily [3]. It localises to the endoplasmic reticulum and mitochondria in neural stem/progenitor cells, and is essential for de novo purine biosynthesis during normal brain development [1,9-10]. Nwd1 is also expressed in the liver where it is involved in modulating liver homeostasis, via a mechanism that involves the Ca²⁺ pump function of SERCA2 (ATP2A2). Nwd1^−/− mice develop pathological features in their livers that resemble those observed in human metabolic dysfunction-associated steatohepatitis (MASH) livers [8]. This discovery suggests Nwd1 (and the other proteins that it interacts with) as a reasonable target for fatty liver disease therapeutic development. Nwd2 has been identified as a paralog of Nwd1.

WD repeat domain 5 Show summary »« Hide summary More detailed page go icon to follow link

References

Show »« Hide

1. Bao T, Yang X, Yu J, Li M, Guo L, Wang Q, Bao Y, Yang Z, Liu Y, Guan T. (2024) NWD1 influences the extension of neuronal axons by regulating microtubule stability. Biochem Biophys Res Commun, 734: 150775. [PMID:39383832]

2. Grebien F, Vedadi M, Getlik M, Giambruno R, Grover A, Avellino R, Skucha A, Vittori S, Kuznetsova E, Smil D et al.. (2015) Erratum: Pharmacological targeting of the Wdr5-MLL interaction in C/EBPα N-terminal leukemia. Nat Chem Biol, 11 (10): 815. [PMID:26379026]

3. Leipe DD, Koonin EV, Aravind L. (2004) STAND, a class of P-loop NTPases including animal and plant regulators of programmed cell death: multiple, complex domain architectures, unusual phyletic patterns, and evolution by horizontal gene transfer. J Mol Biol, 343 (1): 1-28. [PMID:15381417]

4. Li D, Yu X, Kottur J, Gong W, Zhang Z, Storey AJ, Tsai YH, Uryu H, Shen Y, Byrum SD et al.. (2022) Discovery of a dual WDR5 and Ikaros PROTAC degrader as an anti-cancer therapeutic. Oncogene, 41 (24): 3328-3340. [PMID:35525905]

5. SGC. OICR-9429 - a chemical probe for WDR5. Accessed on 03/03/2015. Modified on 04/08/2023. thesgc.org, https://www.thesgc.org/chemical-probes/OICR-9429

6. Teuscher KB, Meyers KM, Wei Q, Mills JJ, Tian J, Alvarado J, Sai J, Van Meveren M, South TM, Rietz TA et al.. (2022) Discovery of Potent Orally Bioavailable WD Repeat Domain 5 (WDR5) Inhibitors Using a Pharmacophore-Based Optimization. J Med Chem, 65 (8): 6287-6312. [PMID:35436124]

7. Teuscher KB, Mills JJ, Tian J, Han C, Meyers KM, Sai J, South TM, Crow MM, Van Meveren M, Sensintaffar JL et al.. (2023) Structure-Based Discovery of Potent, Orally Bioavailable Benzoxazepinone-Based WD Repeat Domain 5 Inhibitors. J Med Chem, 66 (24): 16783-16806. [PMID:38085679]

8. Yamada S, Ogawa H, Funato M, Kato M, Nakadate K, Mizukoshi T, Kawakami K, Kobayashi R, Horii T, Hatada I et al.. (2025) Induction of MASH-like pathogenesis in the Nwd1^-/- mouse liver. Commun Biol, 8 (1): 348. [PMID:40069352]

9. Yamada S, Sakakibara SI. (2018) Expression profile of the STAND protein Nwd1 in the developing and mature mouse central nervous system. J Comp Neurol, 526 (13): 2099-2114. [PMID:30004576]

10. Yamada S, Sato A, Sakakibara SI. (2020) Nwd1 Regulates Neuronal Differentiation and Migration through Purinosome Formation in the Developing Cerebral Cortex. iScience, 23 (5): 101058. [PMID:32344379]

11. Yu X, Li D, Kottur J, Kim HS, Herring LE, Yu Y, Xie L, Hu X, Chen X, Cai L et al.. (2023) Discovery of Potent and Selective WDR5 Proteolysis Targeting Chimeras as Potential Therapeutics for Pancreatic Cancer. J Med Chem, 66 (23): 16168-16186. [PMID:38019706]

How to cite this family page

Database page citation:

WD repeat-containing proteins. Accessed on 10/05/2025. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/FamilyDisplayForward?familyId=903.

Concise Guide to PHARMACOLOGY citation:

Alexander SPH, Kelly E, Mathie AA, Peters JA, Veale EL, Armstrong JF, Buneman OP, Faccenda E, Harding SD, Spedding M, Cidlowski JA, Fabbro D, Davenport AP, Striessnig J, Davies JA et al. (2023) The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets. Br J Pharmacol. 180 Suppl 2:S1-22.