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WD40 repeat

December 15, 2023

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.

WD domain, G-beta repeat
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
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1b9x​, 1b9y​, 1erj​, 1gg2​, 1got​, 1gp2​, 1gxr​, 1nex​, 1nr0​, 1omw​, 1p22​, 1pev​, 1pgu​, 1pi6​, 1s4u​, 1sq9​, 1tbg​, 1u4c​, 1xhm​, 1yfq​, 2bcj​, 2ce8​, 2ce9​, 2trc​

Structure edit

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 edit

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 edit

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:

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 edit

References edit

  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. ^ 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..297N. doi:10.1038/371297a0. PMID 8090199. S2CID 600856.
  3. ^ a b 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.
  4. ^ a b 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. S2CID 20646422.
  5. ^ 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.
  6. ^ 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 edit

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

December 15, 2023
wd40, repeat, also, known, beta, transducin, repeat, short, structural, motif, approximately, amino, acids, often, terminating, tryptophan, aspartic, acid, dipeptide, tandem, copies, these, repeats, typically, fold, together, form, type, circular, solenoid, pr. 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 WD domain G beta repeatRibbon 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 IdentifiersSymbolWD40PfamPF00400Pfam clanCL0186InterProIPR001680PROSITEPDOC00574SCOP21gp2 SCOPe SUPFAMCDDcd00200Available protein structures Pfam structures ECOD PDBRCSB PDB PDBe PDBjPDBsumstructure summaryPDB1b9x 1b9y 1erj 1gg2 1got 1gp2 1gxr 1nex 1nr0 1omw 1p22 1pev 1pgu 1pi6 1s4u 1sq9 1tbg 1u4c 1xhm 1yfq 2bcj 2ce8 2ce9 2trc Contents 1 Structure 2 Function 3 Examples 4 See also 5 References 6 External linksStructure editWD40 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 editWD40 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 editAccording 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 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 WDR11 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 ZFP106Human WDR genes and associated diseases WDR gene other gene names NCBI Entrez Gene ID Human disease associated with mutationsWDR1 AIP1 NORI 1 HEL S 52 9948WDR2 CORO2A IR10 CLIPINB 7464WDR3 DIP2 UTP12 10885WDR4 TRM82 TRMT82 10785WDR5 SWD3 BIG 3 CFAP89 11091WDR6 11180WDR7 TRAG KIAA0541 Rabconnectin 3 beta 23335WDR8 WRAP73 49856WDR9 BRWD1 N143 C21orf107 54014WDR10 IFT122 CED SPG CED1 WDR10p WDR140 55764 Sensenbrenner syndromeWDR11 DR11 HH14 BRWD2 WDR15 55717 Kallmann syndromeWDR12 YTM1 55759WDR13 MG21 64743WDR14 GNB1L GY2 FKSG1 WDVCF DGCRK3 54584WDR15 WDR11WDR16 CFAP52 WDRPUH 146845WDR17 116966WDR18 Ipi3 57418WDR19 ATD5 CED4 DYF 2 ORF26 Oseg6 PWDMP SRTD5 IFT144 NPHP13 57728 Sensenbrenner syndrome Jeune syndromeWDR20 DMR 91833WDR21 DCAF4 WDR21A 26094WDR22 DCAF5 BCRG2 BCRP2 8816WDR23 DCAF11 GL014 PRO2389 80344WDR24 JFP7 C16orf21 84219WDR25 C14orf67 79446WDR26 CDW2 GID7 MIP2 80232WDR27 253769WDR28 GRWD1 CDW4 GRWD RRB1 83743WDR29 SPAG16 PF20 79582WDR30 ATG16L1 IBD10 APG16L ATG16A ATG16L 55054 Crohn s diseaseWDR31 114987WDR32 DCAF10 79269WDR33 NET14 WDC146 55339WDR34 DIC5 FAP133 SRTD11 89891 Jeune syndromeWDR35 CED2 IFTA1 SRTD7 IFT121 57539 Sensenbrenner syndromeWDR36 GLC1G UTP21 TAWDRP TA WDRP 134430 Primary Open Angle GlaucomaWDR37 22884WDR38 401551WDR39 CIAO1 CIA1 9391WDR40A DCAF12 CT102 TCC52 KIAA1892 25853WDR41 MSTP048 55255WDR43 UTP5 NET12 23160WDR44 RPH11 RAB11BP 54521WDR45 JM5 NBIA4 NBIA5 WDRX1 WIPI4 WIPI 4 11152 Beta propeller protein associated neurodegeneration BPAN WDR46 UTP7 BING4 FP221 C6orf11 9277WDR47 NEMITIN KIAA0893 22911WDR48 P80 UAF1 SPG60 57599WDR49 151790WDR50 UTP18 CGI 48 51096WDR52 CFAP44 55779WDR53 348793WDR54 84058WDR55 54853WDR56 IFT80 ATD2 SRTD2 57560 Jeune syndromeWDR57 SNRNP40 SPF38 PRP8BP HPRP8BP PRPF8BP 9410WDR58 THOC6 BBIS fSAP35 79228WDR59 FP977 79726WDR60 SRPS6 SRTD8 FAP163 55112 Jeune syndromeWDR61 SKI8 REC14 80349WDR62 MCPH2 C19orf14 284403 microcephalyWDR63 DIC3 NYD SP29 126820WDR64 128025WDR65 CFAP57 VWS2 149465 Van der Woude syndromeWDR66 CaM IP4 144406WDR67 TBC1D31 Gm85 93594WDR68 DCAF7 AN11 HAN11 SWAN 1 10238WDR69 DAW1 ODA16 164781WDR70 55100WDR71 PAAF1 PAAF Rpn14 80227WDR72 AI2A3 256764 Amelogenesis imperfectaWDR73 HSPC264 84942WDR74 54663WDR75 NET16 UTP17 84128WDR76 CDW14 79968WDR77 p44 MEP50 MEP 50 HKMT1069 Nbla10071 p44 Mep50 79084WDR78 DIC4 79819WDR79 WRAP53 DKCB3 TCAB1 55135WDR80 ATG16L ATG16B 89849WDR81 CAMRQ2 PPP1R166 124997 cerebellar ataxia mental retardation and dysequilibrium syndrome 2WDR82 SWD2 MST107 WDR82A MSTP107 PRO2730 TMEM113 PRO34047 80335WDR83 MORG1 84292WDR84 PAK1IP1 PIP1 MAK11 55003WDR85 DPH7 RRT2 C9orf112 92715WDR86 349136WDR87 NYD SP11 83889WDR88 PQWD 126248WDR89 MSTP050 C14orf150 112840WDR90 C16orf15 C16orf16 C16orf17 C16orf18 C16orf19 197335WDR91 HSPC049 29062WDR92 MONAD 116143WDR93 56964WDR94 AMBRA1 DCAF3 55626WDR96 CFAP43 C10orf79 80217See also editBeta propeller Tomosyn a protein two WD40 domains Protein tandem repeatsReferences edit 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 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 297N doi 10 1038 371297a0 PMID 8090199 S2CID 600856 a b 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 a b 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 S2CID 20646422 Stirnimann CU Petsalaki E Russell RB Muller 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 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 editEukaryotic Linear Motif resource motif class LIG APCC Dbox 1 Eukaryotic Linear Motif resource motif class LIG APCC KENbox 2 Eukaryotic Linear Motif resource motif class LIG COP1 Eukaryotic Linear Motif resource motif class LIG CRL4 Cdt2 1 Eukaryotic Linear Motif resource motif class LIG CRL4 Cdt2 2 Eukaryotic Linear Motif resource motif class LIG EH1 1 Eukaryotic Linear Motif resource motif class LIG GLEBS BUB3 1 Eukaryotic Linear Motif resource motif class LIG RAPTOR TOS 1 Eukaryotic Linear Motif resource motif class LIG SCF FBW7 1 Eukaryotic Linear Motif resource motif class LIG SCF FBW7 2 Eukaryotic Linear Motif resource motif class LIG SCF TrCP1 1 Eukaryotic Linear Motif resource motif class LIG WRPW 1 Eukaryotic Linear Motif resource motif class LIG WRPW 2 Eukaryotic Linear Motif resource motif class TRG ER diArg 1 Eukaryotic Linear Motif resource motif class TRG ER diLys 1 Eukaryotic Linear Motif resource motif class TRG Golgi diPhe 1 Eukaryotic Linear Motif resource motif class TRG PTS2 This article incorporates text from the public domain Pfam and InterPro IPR001680 Retrieved from https en wikipedia org w index php title WD40 repeat amp oldid 1136416673, wikipedia, wiki, book, books, library,

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