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. 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). The WD40 domain is composed of about 40 to 60 amino acids with a glycine and histidine dipeptide near the N-terminus and a tryptophan and aspartic acid dipeptide most commonly at the C-terminus. Two variable regions are present. The 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 seven-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. 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.
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. Human genes encoding proteins containing this domain include: AAAS, AAMP, AHI1, AMBRA1, APAF1, ARPC1A, ARPC1B, ATG16L1, BOP1, BRWD1, BRWD3, BTRC, BUB3, 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, GEMIN5, GNB1, GNB1L, GNB2, GNB2L1, GNB3, GNB4, GNB5, GRWD1, GTF3C2, HERC1, HIRA, HZGJ, IFT121, IFT122, IFT140, IFT172, IFT80, IQWD1, KATNB1, KIF21A, KIF21B, KM-PA-2, KEAP1, LLGL1, LLGL2, LRBA, LRRK1, LRRK2, LRWD1, LYST, MAPKBP1, MED16, MLST8, 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, ZFP106
+Human WDR genes and associated diseases WDR gene other gene names NCBI Entrez Gene ID Human disease associated with mutationsWDR1AIP1; NORI-1; HEL-S-529948WDR2CORO2A; IR10; CLIPINB7464WDR3DIP2; UTP1210885WDR4TRM82; TRMT8210785WDR5SWD3; BIG-3; CFAP8911091WDR611180WDR7TRAG; KIAA0541; Rabconnectin 3 beta23335WDR8WRAP7349856WDR9BRWD1; N143; C21orf10754014WDR10IFT122; CED; SPG; CED1; WDR10p; WDR14055764Sensenbrenner syndromeWDR11DR11; HH14; BRWD2; WDR1555717Kallmann syndromeWDR12YTM155759WDR13MG2164743WDR14GNB1L; GY2; FKSG1; WDVCF; DGCRK354584WDR15WDR11 WDR16CFAP52; WDRPUH146845WDR17116966WDR18Ipi357418WDR19ATD5; CED4; DYF-2; ORF26; Oseg6; PWDMP; SRTD5; IFT144; NPHP1357728Sensenbrenner syndrome, Jeune syndromeWDR20DMR91833WDR21DCAF4; WDR21A26094WDR22DCAF5; BCRG2; BCRP28816WDR23DCAF11; GL014; PRO238980344WDR24JFP7; C16orf2184219WDR25C14orf6779446WDR26CDW2; GID7; MIP280232WDR27253769WDR28GRWD1; CDW4; GRWD; RRB183743WDR29SPAG16; PF2079582WDR30ATG16L1; IBD10; APG16L; ATG16A; ATG16L55054Crohn’s diseaseWDR31114987WDR32DCAF1079269WDR33NET14; WDC14655339WDR34DIC5; FAP133; SRTD1189891Jeune syndromeWDR35CED2; IFTA1; SRTD7; IFT12157539Sensenbrenner syndromeWDR36GLC1G; UTP21; TAWDRP; TA-WDRP134430Primary Open Angle GlaucomaWDR3722884WDR38401551WDR39CIAO1; CIA19391WDR40ADCAF12; CT102; TCC52; KIAA189225853WDR41MSTP04855255WDR43UTP5; NET1223160WDR44RPH11; RAB11BP54521WDR45JM5; NBIA4; NBIA5; WDRX1; WIPI4; WIPI-411152Beta-propeller protein-associated neurodegeneration (BPAN)WDR46UTP7; BING4; FP221; C6orf119277WDR47NEMITIN; KIAA089322911WDR48P80; UAF1; SPG6057599WDR49151790WDR50UTP18; CGI-4851096WDR52CFAP4455779WDR53348793WDR5484058WDR5554853WDR56IFT80; ATD2; SRTD257560Jeune syndromeWDR57SNRNP40; SPF38; PRP8BP; HPRP8BP; PRPF8BP9410WDR58THOC6; BBIS; fSAP3579228WDR59FP97779726WDR60SRPS6; SRTD8; FAP16355112Jeune syndromeWDR61SKI8; REC1480349WDR62MCPH2; C19orf14284403microcephalyWDR63DIC3; NYD-SP29126820WDR64128025WDR65CFAP57; VWS2149465Van der Woude syndromeWDR66CaM-IP4144406WDR67TBC1D31; Gm8593594WDR68DCAF7; AN11; HAN11; SWAN-110238WDR69DAW1; ODA16164781WDR7055100WDR71PAAF1; PAAF; Rpn1480227WDR72AI2A3256764Amelogenesis imperfectaWDR73HSPC26484942WDR7454663WDR75NET16; UTP17 84128WDR76CDW1479968WDR77p44; MEP50; MEP-50; HKMT1069; Nbla10071; p44/Mep5079084WDR78DIC479819WDR79WRAP53; DKCB3; TCAB155135WDR80ATG16L; ATG16B89849WDR81CAMRQ2; PPP1R166124997cerebellar ataxia, mental retardation, and dysequilibrium syndrome-2WDR82SWD2; MST107; WDR82A; MSTP107; PRO2730; TMEM113; PRO3404780335WDR83MORG184292WDR84PAK1IP1; PIP1; MAK1155003WDR85DPH7; RRT2; C9orf11292715WDR86349136WDR87NYD-SP1183889WDR88PQWD126248WDR89MSTP050; C14orf150112840WDR90C16orf15; C16orf16; C16orf17; C16orf18; C16orf19197335WDR91HSPC04929062WDR92MONAD116143WDR9356964WDR94AMBRA1; DCAF355626WDR96CFAP43; C10orf7980217
See also Beta-propeller Protein tandem repeats
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