WD-40 repeat family

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Associate Editor(s)-in-Chief: Henry A. Hoff

WD domain, G-beta repeat
File:1erj 7bladed beta propeller.png
Ribbon diagram of the C-terminal WD40 domain of Tup1 (a transcriptional corepressor in yeast), which adopts a 7-bladed beta-propeller fold. Ribbon is colored from blue (N-terminus) to red (C-terminus).[1]
Identifiers
SymbolWD40
PfamPF00400
Pfam clanCL0186
InterProIPR001680
PROSITEPDOC00574
SCOP1gp2
SUPERFAMILY1gp2
CDDcd00200

"Receptor for activated C kinase (RACK1) is a highly conserved, eukaryotic protein of the WD-40 repeat family. [...] During Phaseolus vulgaris root development, RACK1 (PvRACK1) mRNA expression was induced by auxins, abscissic acid, cytokinin, and gibberellic acid."[2]

The WD40 repeat (also known as the WD or beta-transducin repeat) is a short structural motif of approximately 40 amino acids, often terminating in a tryptophan-aspartic acid (W-D) dipeptide.[3]

Structure

WD40 domain-containing proteins have 4 to 16 repeating units, all of which are thought to form a circularised beta-propeller structure (see figure to the right).[4][5]

Function

WD40-repeat proteins are a large family found in all eukaryotes and are implicated in a variety of functions ranging from signal transduction and transcription regulation to cell cycle control, autophagy and apoptosis.[6] The underlying common function of all WD40-repeat proteins is coordinating multi-protein complex assemblies, where the repeating units serve as a rigid scaffold for protein interactions. The specificity of the proteins is determined by the sequences outside the repeats themselves. Examples of such complexes are G proteins (beta subunit is a beta-propeller), TAFII transcription factor, and E3 ubiquitin ligase.[4][5]

Protein family

According to the initial analysis of the human genome WD40 repeats are the eighth largest family of proteins. In all 277 proteins were identified to contain them.[7] Human genes encoding proteins containing this domain include:

Human WDR genes and associated diseases
WDR gene other gene names NCBI Entrez
Gene ID
Human disease associated with mutations
WDR1 AIP1; NORI-1; HEL-S-52 9948
WDR2 CORO2A; IR10; CLIPINB 7464
WDR3 DIP2; UTP12 10885
WDR4 TRM82; TRMT82 10785
WDR5 SWD3; BIG-3; CFAP89 11091
WDR6 11180
WDR7 TRAG; KIAA0541; Rabconnectin 3 beta 23335
WDR8 WRAP73 49856
WDR9 BRWD1; N143; C21orf107 54014
WDR10 IFT122; CED; SPG; CED1; WDR10p; WDR140 55764 Sensenbrenner syndrome
WDR11 DR11; HH14; BRWD2; WDR15 55717 Kallmann syndrome
WDR12 YTM1 55759
WDR13 MG21 64743
WDR14 GNB1L; GY2; FKSG1; WDVCF; DGCRK3 54584
WDR15 WDR11
WDR16 CFAP52; WDRPUH 146845
WDR17 116966
WDR18 Ipi3 57418
WDR19 ATD5; CED4; DYF-2; ORF26; Oseg6; PWDMP; SRTD5; IFT144; NPHP13 57728 Sensenbrenner syndrome, Jeune syndrome
WDR20 DMR 91833
WDR21 DCAF4; WDR21A 26094
WDR22 DCAF5; BCRG2; BCRP2 8816
WDR23 DCAF11; GL014; PRO2389 80344
WDR24 JFP7; C16orf21 84219
WDR25 C14orf67 79446
WDR26 CDW2; GID7; MIP2 80232
WDR27 253769
WDR28 GRWD1; CDW4; GRWD; RRB1 83743
WDR29 SPAG16; PF20 79582
WDR30 ATG16L1; IBD10; APG16L; ATG16A; ATG16L 55054 Crohn’s disease
WDR31 114987
WDR32 DCAF10 79269
WDR33 NET14; WDC146 55339
WDR34 DIC5; FAP133; SRTD11 89891 Jeune syndrome
WDR35 CED2; IFTA1; SRTD7; IFT121 57539 Sensenbrenner syndrome
WDR36 GLC1G; UTP21; TAWDRP; TA-WDRP 134430 Primary Open Angle Glaucoma
WDR37 22884
WDR38 401551
WDR39 CIAO1; CIA1 9391
WDR40A DCAF12; CT102; TCC52; KIAA1892 25853
WDR41 MSTP048 55255
WDR43 UTP5; NET12 23160
WDR44 RPH11; RAB11BP 54521
WDR45 JM5; NBIA4; NBIA5; WDRX1; WIPI4; WIPI-4 11152 Beta-propeller protein-associated neurodegeneration (BPAN)
WDR46 UTP7; BING4; FP221; C6orf11 9277
WDR47 NEMITIN; KIAA0893 22911
WDR48 P80; UAF1; SPG60 57599
WDR49 151790
WDR50 UTP18; CGI-48 51096
WDR52 CFAP44 55779
WDR53 348793
WDR54 84058
WDR55 54853
WDR56 IFT80; ATD2; SRTD2 57560 Jeune syndrome
WDR57 SNRNP40; SPF38; PRP8BP; HPRP8BP; PRPF8BP 9410
WDR58 THOC6; BBIS; fSAP35 79228
WDR59 FP977 79726
WDR60 SRPS6; SRTD8; FAP163 55112 Jeune syndrome
WDR61 SKI8; REC14 80349
WDR62 MCPH2; C19orf14 284403 microcephaly
WDR63 DIC3; NYD-SP29 126820
WDR64 128025
WDR65 CFAP57; VWS2 149465 Van der Woude syndrome
WDR66 CaM-IP4 144406
WDR67 TBC1D31; Gm85 93594
WDR68 DCAF7; AN11; HAN11; SWAN-1 10238
WDR69 DAW1; ODA16 164781
WDR70 55100
WDR71 PAAF1; PAAF; Rpn14 80227
WDR72 AI2A3 256764 Amelogenesis imperfecta
WDR73 HSPC264 84942
WDR74 54663
WDR75 NET16; UTP17 84128
WDR76 CDW14 79968
WDR77 p44; MEP50; MEP-50; HKMT1069; Nbla10071; p44/Mep50 79084
WDR78 DIC4 79819
WDR79 WRAP53; DKCB3; TCAB1 55135
WDR80 ATG16L; ATG16B 89849
WDR81 CAMRQ2; PPP1R166 124997 cerebellar ataxia, mental retardation, and dysequilibrium syndrome-2
WDR82 SWD2; MST107; WDR82A; MSTP107; PRO2730; TMEM113; PRO34047 80335
WDR83 MORG1 84292
WDR84 PAK1IP1; PIP1; MAK11 55003
WDR85 DPH7; RRT2; C9orf112 92715
WDR86 349136
WDR87 NYD-SP11 83889
WDR88 PQWD 126248
WDR89 MSTP050; C14orf150 112840
WDR90 C16orf15; C16orf16; C16orf17; C16orf18; C16orf19 197335
WDR91 HSPC049 29062
WDR92 MONAD 116143
WDR93 56964
WDR94 AMBRA1; DCAF3 55626
WDR96 CFAP43; C10orf79 80217

Hypotheses

  1. A1BG has no regulatory elements in either promoter for the WD-40 repeat family proteins.
  2. A1BG is not transcribed by a regulatory element for the WD-40 repeat family proteins.
  3. No regulatory element for the WD-40 repeat family proteins participates in the transcription of A1BG.

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

See also

References

  1. PDB: 1erj​; Sprague ER, Redd MJ, Johnson AD, Wolberger C (June 2000). "Structure of the C-terminal domain of Tup1, a corepressor of transcription in yeast". EMBO J. 19 (12): 3016–27. doi:10.1093/emboj/19.12.3016. PMC 203344. PMID 10856245.
  2. Tania Islas-Flores, Gabriel Guillén, Xóchitl Alvarado-Affantranger, Miguel Lara-Flores, Federico Sánchez, and Marco A. Villanueva (2011). "PvRACK1 Loss-of-Function Impairs Cell Expansion and Morphogenesis in Phaseolus vulgaris L. Root Nodules". Molecular Plant-Microbe Interactions. 24 (7): 819–826. doi:10.1094/MPMI-11-10-0261. Retrieved 25 April 2021.
  3. Neer EJ, Schmidt CJ, Nambudripad R, Smith TF (September 1994). "The ancient regulatory-protein family of WD-repeat proteins". Nature. 371 (6495): 297–300. Bibcode:1994Natur.371..297N6 Check |bibcode= length (help). doi:10.1038/371297a0. PMID 8090199.
  4. 4.0 4.1 Smith TF, Gaitatzes C, Saxena K, Neer EJ (May 1999). "The WD40 repeat: a common architecture for diverse functions". Trends Biochem. Sci. 24 (5): 181–5. doi:10.1016/S0968-0004(99)01384-5. PMID 10322433.
  5. 5.0 5.1 Li D, Roberts R (December 2001). "WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases". Cell. Mol. Life Sci. 58 (14): 2085–97. doi:10.1007/PL00000838. PMID 11814058.
  6. Stirnimann CU, Petsalaki E, Russell RB, Müller CW (May 2010). "WD40 proteins propel cellular networks". Trends Biochem. Sci. 35 (10): 565–74. doi:10.1016/j.tibs.2010.04.003. PMID 20451393.
  7. Lander ES, Linton LM, Birren B, et al. (February 2001). "Initial sequencing and analysis of the human genome" (PDF). Nature. 409 (6822): 860–921. doi:10.1038/35057062. PMID 11237011.

External links