WD40 repeat

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
Symbol	WD40
Pfam	PF00400
Pfam clan	CL0186
InterPro	IPR001680
PROSITE	PDOC00574
SCOP2	1gp2 / SCOPe / SUPFAM
CDD	cd00200
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary PDB 1b9x ​, 1b9y ​, 1erj ​, 1gg2 ​, 1got ​, 1gp2 ​, 1gxr ​, 1nex ​, 1nr0 ​, 1omw ​, 1p22 ​, 1pev ​, 1pgu ​, 1pi6 ​, 1s4u ​, 1sq9 ​, 1tbg ​, 1u4c ​, 1xhm ​, 1yfq ​, 2bcj ​, 2ce8 ​, 2ce9 ​, 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. ^[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 about 40 to 60 ^[4] 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. ^{[3] [4]}

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, 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

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

• Beta-propeller
• Tomosyn, a protein two WD40 domains
• Protein tandem repeats

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. 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. 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. 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. PMC   11337334 . 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

• Eukaryotic 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