WD40 repeat

{{short description|Short protein motif that forms a solenoid domain}} {{Distinguish|WD-40|}} {{Pfam_box | Symbol = WD40 | Name = WD domain, G-beta repeat | image = 1erj 7bladed beta propeller.png | width = | caption = 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).<ref name="pmid10856245">{{PDB|1erj}}; {{cite journal | vauthors = Sprague ER, Redd MJ, Johnson AD, Wolberger C | title = Structure of the C-terminal domain of Tup1, a corepressor of transcription in yeast | journal = EMBO J. | volume = 19 | issue = 12 | pages = 3016–27 |date=June 2000 | pmid = 10856245 | pmc = 203344 | doi = 10.1093/emboj/19.12.3016 }}</ref> | Pfam = PF00400 | Pfam_clan = CL0186 | InterPro = IPR001680 | SMART = | PROSITE = PDOC00574 | SCOP = 1gp2 | TCDB = | CDD = cd00200 | OPM family = | OPM protein = | PDB = {{PDB2|1b9x}}, {{PDB2|1b9y}}, {{PDB2|1erj}}, {{PDB2|1gg2}}, {{PDB2|1got}}, {{PDB2|1gp2}}, {{PDB2|1gxr}}, {{PDB2|1nex}}, {{PDB2|1nr0}}, {{PDB2|1omw}}, {{PDB2|1p22}}, {{PDB2|1pev}}, {{PDB2|1pgu}}, {{PDB2|1pi6}}, {{PDB2|1s4u}}, {{PDB2|1sq9}}, {{PDB2|1tbg}}, {{PDB2|1u4c}}, {{PDB2|1xhm}}, {{PDB2|1yfq}}, {{PDB2|2bcj}}, {{PDB2|2ce8}}, {{PDB2|2ce9}}, {{PDB2|2trc}} }}

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.<ref name="pmid8090199">{{cite journal | vauthors = Neer EJ, Schmidt CJ, Nambudripad R, Smith TF | title = The ancient regulatory-protein family of WD-repeat proteins | journal = Nature | volume = 371 | issue = 6495 | pages = 297–300 |date=September 1994 | pmid = 8090199 | doi = 10.1038/371297a0 | bibcode = 1994Natur.371..297N | s2cid = 600856 }}</ref> 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).<ref name="pmid10322433">{{cite journal | vauthors = Smith TF, Gaitatzes C, Saxena K, Neer EJ | title = The WD40 repeat: a common architecture for diverse functions | journal = Trends Biochem. Sci. | volume = 24 | issue = 5 | pages = 181–5 |date=May 1999 | pmid = 10322433 | doi = 10.1016/S0968-0004(99)01384-5| doi-access = free }}</ref><ref name="pmid11814058">{{cite journal | vauthors = Li D, Roberts R | title = WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases | journal = Cell. Mol. Life Sci. | volume = 58 | issue = 14 | pages = 2085–97 |date=December 2001 | pmid = 11814058 | doi = 10.1007/PL00000838| s2cid = 20646422 | pmc = 11337334 }}</ref> The WD40 domain is composed of about 40 to 60<ref name="pmid11814058"/> 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.<ref name="pmid10322433"/><ref name="pmid11814058"/>

==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.<ref name="pmid20451393">{{cite journal | vauthors = Stirnimann CU, Petsalaki E, Russell RB, Müller CW | title = WD40 proteins propel cellular networks. | journal = Trends Biochem. Sci. | volume = 35 | issue = 10 | pages = 565–74 |date=May 2010 | pmid = 20451393 | doi = 10.1016/j.tibs.2010.04.003}}</ref> 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.<ref name="pmid10322433"/><ref name="pmid11814058"/>

==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.<ref name="pmid11237011">{{cite journal |vauthors=Lander ES, Linton LM, Birren B, etal |title=Initial sequencing and analysis of the human genome |journal=Nature |volume=409 |issue=6822 |pages=860–921 |date=February 2001 |pmid=11237011 |doi=10.1038/35057062 |url=https://deepblue.lib.umich.edu/bitstream/2027.42/62798/1/409860a0.pdf|doi-access=free }}</ref> 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, * ZFP106

{| class="wikitable" |+Human WDR genes and associated diseases |- ! WDR gene !! other gene names !! NCBI Entrez<br> 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== * Beta-propeller * Tomosyn, a protein two WD40 domains * Protein tandem repeats

==References== {{Reflist}}

==External links== * {{ELM|LIG_APCC_Dbox_1}} * {{ELM|LIG_APCC_KENbox_2}} * {{ELM|LIG_COP1}} * {{ELM|LIG_CRL4_Cdt2_1}} * {{ELM|LIG_CRL4_Cdt2_2}} * {{ELM|LIG_EH1_1}} * {{ELM|LIG_GLEBS_BUB3_1}} * {{ELM|LIG_RAPTOR_TOS_1}} * {{ELM|LIG_SCF_FBW7_1}} * {{ELM|LIG_SCF_FBW7_2}} * {{ELM|LIG_SCF-TrCP1_1}} * {{ELM|LIG_WRPW_1}} * {{ELM|LIG_WRPW_2}} * {{ELM|TRG_ER_diArg_1}} * {{ELM|TRG_ER_diLys_1}} * {{ELM|TRG_Golgi_diPhe_1}} * {{ELM|TRG_PTS2}}