Biology:WD40 repeat

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WD domain, G-beta repeat
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
SCOP21gp2 / SCOPe / SUPFAM
CDDcd00200

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.[2] Tandem copies of these repeats typically fold together to form a type of circular solenoid protein domain called the WD40 domain.

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).[3][4] The WD40 domain is composed of several repeats, a variable region of around 20 residues at the beginning followed by a more common repeated set of residues. These repeats typically form a four stranded anti-parallel beta sheet or blade. These blades come together to form a propeller with the most common being a 7 bladed beta propeller. The blades interlock so that the last beta strand of one repeat forms with the first three of the next repeat to form the 3D blade structure.

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.[5] 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.[3][4]

Examples

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.[6] Human genes encoding proteins containing this domain include:

  • AAAS, AAMP, AHI1, AMBRA1, APAF1, ARPC1A, ARPC1B, ATG16L1,
  • BOP1, BRWD1, BRWD2, BRWD3, BTRC, BUB3,
  • C6orf11, CDC20, CDC40, CDRT1, CHAF1B, CIAO1, CIRH1A, COPA, COPB2, CORO1A, CORO1B, CORO1C, CORO2A, CORO2B, CORO6, CORO7, CSTF1,
  • DDB2, DENND3, DMWD, DMXL1, DMXL2, DNAI1, DNAI2, DNCI1, DTL, DYNC1I1, DYNC1I2, EDC4,
  • EED, EIF3S2, ELP2, EML1, EML2, EML3, EML4, EML4-ALK, EML5, ERCC8,
  • FBXW10, FBXW11, FBXW2, FBXW4, FBXW5, FBXW7, FBXW8, FBXW9, FZR1,
  • GBL, GEMIN5, GNB1, GNB1L, GNB2, GNB2L1, GNB3, GNB4, GNB5, GRWD1, GTF3C2,
  • HERC1, HIRA, HZGJ,
  • IFT121, IFT122, IFT140, IFT172, IFT80, IQWD1,
  • KATNB1, KIAA1336, KIF21A, KIF21B, KM-PA-2,
  • KEAP1,
  • LLGL1, LLGL2, LRBA, LRRK1, LRRK2, LRWD1, LYST,
  • MAPKBP1, MED16, MORG1,
  • NBEA, NBEAL1, NEDD1, NLE1, NSMAF, NUP37, NUP43, NWD1,
  • PAAF1, PAFAH1B1, PAK1IP1, PEX7, PHIP, PIK3R4, PLAA, PLRG1, PPP2R2A, PPP2R2B, PPP2R2C, PPP2R2D, PPWD1, PREB, PRPF19, PRPF4, PWP1, PWP2,
  • RAE1, RPTOR, RBBP4, RBBP5, RBBP7, RFWD2, RFWD3, RRP9,
  • SCAP, SEC13, SEC31A, SEC31B, SEH1L, SHKBP1, SMU1, SPAG16, SPG, STRAP, STRN, STRN3, STRN4, STXBP5, STXBP5L,
  • TAF5, TAF5L, TBL1X, TBL1XR1, TBL1Y, TBL2, TBL3, TEP1, THOC3, THOC6, TLE1, TLE2, TLE3, TLE4, TLE6, TRAF7, TSSC1, TULP4, TUWD12,
  • UTP15, UTP18,
  • WAIT1, WDF3, WDFY1, WDFY2, WDFY3, WDFY4, WDHD1, WDR1, WDR10, WDR12, WDR13, WDR16, WDR17, WDR18, WDR19, WDR20, WDR21A, WDR21C, WDR22, WDR23, WDR24, WDR25, WDR26, WDR27, WDR3, WDR31, WDR32, WDR33, WDR34, WDR35, WDR36, WDR37, WDR38, WDR4, WDR40A, WDR40B, WDR40C, WDR41, WDR42A, WDR42B, WDR43, WDR44, WDR46, WDR47, WDR48, WDR49, WDR5, WDR51A, WDR51B, WDR52, WDR53, WDR54, WDR55, WDR57, WDR59, WDR5B, WDR6, WDR60, WDR61, WDR62, WDR63, WDR64, WDR65, WDR66, WDR67, WDR68, WDR69, WDR7, WDR70, WDR72, WDR73, WDR74, WDR75, WDR76, WDR77, WDR78, WDR79, WDR8, WDR81, WDR82, WDR85, WDR86, WDR88, WDR89, WDR90, WDR91, WDR92, WDSOF1, WDSUB1, WDTC1, WSB1, WSB2,
  • ZFP106
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

See also

References

  1. ↑ PDB: 1erj​; "Structure of the C-terminal domain of Tup1, a corepressor of transcription in yeast". EMBO J. 19 (12): 3016–27. June 2000. doi:10.1093/emboj/19.12.3016. PMID 10856245. 
  2. ↑ "The ancient regulatory-protein family of WD-repeat proteins". Nature 371 (6495): 297–300. September 1994. doi:10.1038/371297a0. PMID 8090199. 
  3. ↑ 3.0 3.1 "The WD40 repeat: a common architecture for diverse functions". Trends Biochem. Sci. 24 (5): 181–5. May 1999. doi:10.1016/S0968-0004(99)01384-5. PMID 10322433. 
  4. ↑ 4.0 4.1 "WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases". Cell. Mol. Life Sci. 58 (14): 2085–97. December 2001. doi:10.1007/PL00000838. PMID 11814058. 
  5. ↑ "WD40 proteins propel cellular networks.". Trends Biochem. Sci. 35 (10): 565–74. May 2010. doi:10.1016/j.tibs.2010.04.003. PMID 20451393. 
  6. ↑ "Initial sequencing and analysis of the human genome". Nature 409 (6822): 860–921. February 2001. doi:10.1038/35057062. PMID 11237011. 

External links

This article incorporates text from the public domain Pfam and InterPro: IPR001680




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