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9287  structures 3496  species 0  interactions 938410  sequences 8313  architectures

Family: WD40 (PF00400)

Summary: WD domain, G-beta repeat

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This is the Wikipedia entry entitled "Beta-propeller". More...

Beta-propeller Edit Wikipedia article

WD domain, G-beta repeat
1erj 7bladed beta propeller.png
Ribbon diagram of the C-terminal WD40 domain of Tup1 (a transcriptional co-repressor in yeast), which adopts a 7-bladed beta-propeller fold. Ribbon is colored from blue (N-terminus) to red (C-terminus). PDB 1erj [1]
Identifiers
SymbolWD40
PfamPF00400
Pfam clanCL0186
InterProIPR001680
PROSITEPDOC00574
SCOP21gp2 / SCOPe / SUPFAM
CDDcd00200

In structural biology, a beta-propeller (β-propeller) is a type of all-β protein architecture characterized by 4 to 8 highly symmetrical blade-shaped beta sheets arranged toroidally around a central axis. Together the beta-sheets form a funnel-like active site.

Structure

Each beta-sheet typically has four anti-parallel β-strands arranged in the beta-zigzag motif.[2] The strands are twisted so that the first and fourth strands are almost perpendicular to each other.[3] There are five classes of beta-propellers, each arrangement being a highly symmetrical structure with 4–8 beta sheets, all of which generally form a central tunnel that yields pseudo-symmetric axes.[2]

While, the protein's official active site for ligand-binding is formed at one end of the central tunnel by loops between individual beta-strands, protein-protein interactions can occur at multiple areas around the domain. Depending on the packing and tilt of the beta-sheets and beta-strands, the beta-propeller may have a central pocket in place of a tunnel.[4]

The beta-propeller structure is stabilized mainly through hydrophobic interactions of the beta-sheets, while additional stability may come from hydrogen bonds formed between the beta-sheets of the C- and N-terminal ends. In effect this closes the circle which can occur even more strongly in 4-bladed proteins via a disulfide bond.[2] The chaperones Hsp70 and CCT have been shown to sequentially bind nascent beta-propellers as they emerge from the ribosome. These chaperones prevent non-native inter-blade interactions from forming until the entire beta-propeller is synthesized.[5] Many beta-propellers are dependent on CCT for expression.[6][7][8] In at least one case, ions have been shown to increase stability by binding deep in the central tunnel of the beta-propeller.[4]

Murzin proposed a geometric model to describe the structural principles of the beta propeller.[9] According to this model the seven bladed propeller was the most favored arrangement in geometric terms.

Despite its highly conserved nature, beta-propellers are well known for their plasticity. Beyond having a variety of allowed beta-sheets per domain, it can also accommodate other domains into its beta-sheets. Additionally, there are proteins that have shown variance in the number of beta-strands per beta-sheet. Rather than having the typical four beta-strands in a sheet, beta-lactamase inhibitor protein-II only has three beta-strands per sheet while the phytase of Bacillus subtilis has five beta-strands per beta-sheet.[2]

Function

Due to its structure and plasticity, protein-protein interactions can form with the top, bottom, central channel, and side faces of the beta-propeller.[4] The function of the propeller can vary based on the blade number. Four-bladed beta-propellers function mainly as transport proteins, and because of its structure, they have a conformation that is favorable for substrate binding.[4] Unlike larger beta-propellers, four-bladed beta-propellers usually cannot perform catalysis themselves, but act instead to aid in catalysis by performing the aforementioned functions. Five-bladed propellers can act as transferases, hydrolases, and sugar binding proteins.[4] Six- and seven-bladed propellers perform a much broader variety of functions in comparison to four- and five-bladed propellers. These functions can include acting as ligand-binding proteins, hydrolases, lyases, isomerases, signaling proteins, structural proteins, and oxidoreductases.[4]

Variations in the larger (five- to eight-bladed) beta-propellers can allow for even more specific functions. This is the case with the C-terminal region of GyrA which expresses a positively charged surface ideal for binding DNA. Two alpha-helices coming out of the six-bladed beta-propeller of serum paraoxonase may provide a hydrophobic region ideal for anchoring membranes. DNA damage-binding protein 1 has three beta-propellers, in which the connection between two of the propellers is inserted into the third propeller potentially allowing for its unique function.[4]

Clinical Significance

  • Beta-propeller protein-associated neurodegeneration (BPAN) is a condition characterized by early onset seizures, developmental delays, and intellectual disability. With aging, muscle and cognitive degeneration may also occur. Variants of the WDR45 gene have been identified in both males and females with this condition.[10]
  • Familial hypercholesterolemia is a human genetic disease caused by mutations to the gene that encodes low density lipoprotein receptor (LDLR), a protein which has at least one beta-propeller. This disease causes increased concentrations of low-density lipoprotein (LDL) and cholesterol which can lead to further consequences such as coronary atherosclerosis. Confirmed mutations have been shown to interfere with hydrogen bonding between blades of the beta-propeller.[2]
  • The beta-propeller has been used in protein engineering in several cases. Yoshida et al., for example, worked with glucose dehydrogenase (GDH), having a six-blade beta-propeller, to make an enzyme ideal for use as a glucose sensor. They succeeded in engineering a GDH chimera which had a higher thermostability, higher co-factor binding stability, and increased substrate specificity. These properties were attributed to increased hydrophobic interactions due to mutations at the C-terminus of the beta-propeller.[2]
  • The beta-propeller domain of the influenza virus neuraminidase are often used for drug design. Through study of this enzyme, researchers have developed influenza neuraminidase inhibitors which effectively block the influenza neuraminidase and consequently slowing or stopping the progression of the influenza infection.[2]

Examples

  • The influenza virus protein viral neuraminidase is a six-bladed beta-propeller protein whose active form is a tetramer.[11] It is one of two proteins present in the viral envelope and catalyzes the cleavage of sialic acid moieties from cell-membrane proteins to aid in the targeting of newly produced virions to previously uninfected cells.[12]
  • WD40 repeats, also known as beta-transducin repeats, are short fragments found primarily in eukaryotes.[13][14] They usually form beta-propellers with 7–8 blades, but have also been shown to form structural domains with 4 to 16 repeated units critical for protein–protein interactions. WD40 protein motifs are involved in a variety of functions including signal transduction, transcription regulation, and regulation of the cell cycle. They also work as sites for protein-protein interactions, and can even play a role in the assembly of protein complexes. Specificity of these structural domains are determined by the sequence of the protein outside of itself.[15]
  • A beta-propeller is a critical component of LDLR and aids in a pH based conformational change. At neutral pH the LDLR is in an extended linear conformation and can bind ligands (PCSK9). At acidic pH the linear conformation changes to a hairpin structure such that ligand binding sites bind to the beta-propeller, preventing ligand binding.[16][17]
  • Beta-propeller phytases consist of a six-bladed β-propeller structure. Phytases are phosphatases that can hydrolyze the ester bonds of phytate, the major form of phosphate storage in plants. Through this process, phosphate that is normally inaccessible to livestock becomes available. Most livestock feed has added inorganic phosphate, which when excreted, can cause environmental pollution. The addition of phytase instead of phosphate into livestock feed would allow for animals to break down the phosphate already available in the plant matter. This would theoretically produce less pollution as less of the excess phosphate would be excreted.[18]

Domains

Repeat domains known to fold into a beta-propeller include WD40, YWTD, Kelch, YVTN, RIVW (PD40), and many more. Their sequences tend to group together, suggesting a close evolutionary link. They are also related to many beta-containing domains.[19]

References

  1. ^ Sprague ER, Redd MJ, Johnson AD, Wolberger C (June 2000). "Structure of the C-terminal domain of Tup1, a corepressor of transcription in yeast". The EMBO Journal. 19 (12): 3016–27. doi:10.1093/emboj/19.12.3016. PMC 203344. PMID 10856245.
  2. ^ a b c d e f g "Beta-propellers: Associated Functions and their Role in Human Diseases". ResearchGate. Retrieved 2018-11-17.
  3. ^ Kuriyan, Konforti, Wemmer, John, Boyana, David (2013). The molecules of life: physical and chemical principles. New York: Garland Science. pp. 163–164. ISBN 9780815341888.CS1 maint: multiple names: authors list (link)
  4. ^ a b c d e f g Chen CK, Chan NL, Wang AH (October 2011). "The many blades of the β-propeller proteins: conserved but versatile". Trends in Biochemical Sciences. 36 (10): 553–61. doi:10.1016/j.tibs.2011.07.004. PMID 21924917.
  5. ^ Stein KC, Kriel A, Frydman J (July 2019). "Nascent Polypeptide Domain Topology and Elongation Rate Direct the Cotranslational Hierarchy of Hsp70 and TRiC/CCT". Molecular Cell. 75 (6): 1117–1130.e5. doi:10.1016/j.molcel.2019.06.036. PMC 6953483. PMID 31400849.
  6. ^ Plimpton RL, Cuéllar J, Lai CW, Aoba T, Makaju A, Franklin S, et al. (February 2015). "Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly". Proceedings of the National Academy of Sciences of the United States of America. 112 (8): 2413–8. Bibcode:2015PNAS..112.2413P. doi:10.1073/pnas.1419595112. PMC 4345582. PMID 25675501.
  7. ^ Cuéllar J, Ludlam WG, Tensmeyer NC, Aoba T, Dhavale M, Santiago C, et al. (June 2019). "Structural and functional analysis of the role of the chaperonin CCT in mTOR complex assembly". Nature Communications. 10 (1): 2865. Bibcode:2019NatCo..10.2865C. doi:10.1038/s41467-019-10781-1. PMC 6599039. PMID 31253771.
  8. ^ Ludlam, WG; Aoba, T; Cuéllar, J; Bueno-Carrasco, MT; Makaju, A; Moody, JD; Franklin, S; Valpuesta, JM; Willardson, BM (2019-11-01). "Molecular architecture of the Bardet-Biedl syndrome protein 2-7-9 subcomplex". The Journal of Biological Chemistry. 294 (44): 16385–16399. doi:10.1074/jbc.RA119.010150. hdl:10261/240872. PMC 6827290. PMID 31530639.
  9. ^ Murzin AG (October 1992). "Structural principles for the propeller assembly of beta-sheets: the preference for seven-fold symmetry". Proteins. 14 (2): 191–201. doi:10.1002/prot.340140206. PMID 1409568. S2CID 22228091.
  10. ^ Gregory A, Kurian MA, Haack T, Hayflick SJ, Hogarth P (1993). Adam MP, Ardinger HH, Pagon RA, Wallace SE (eds.). Beta-Propeller Protein-Associated Neurodegeneration. GeneReviews®. University of Washington, Seattle. PMID 28211668. Retrieved 2018-11-20.
  11. ^ Air GM (July 2012). "Influenza neuraminidase". Influenza and Other Respiratory Viruses. 6 (4): 245–56. doi:10.1111/j.1750-2659.2011.00304.x. PMC 3290697. PMID 22085243.
  12. ^ Matrosovich MN, Matrosovich TY, Gray T, Roberts NA, Klenk HD (November 2004). "Neuraminidase is important for the initiation of influenza virus infection in human airway epithelium". Journal of Virology. 78 (22): 12665–7. doi:10.1128/JVI.78.22.12665-12667.2004. PMC 525087. PMID 15507653.
  13. ^ 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.
  14. ^ Smith TF, Gaitatzes C, Saxena K, Neer EJ (May 1999). "The WD repeat: a common architecture for diverse functions". Trends in Biochemical Sciences. 24 (5): 181–5. doi:10.1016/S0968-0004(99)01384-5. PMID 10322433.
  15. ^ EMBL-EBI, InterPro. "WD40-like Beta Propeller (IPR011659) < InterPro < EMBL-EBI". www.ebi.ac.uk. Retrieved 2018-11-19.
  16. ^ Zhang DW, Garuti R, Tang WJ, Cohen JC, Hobbs HH (September 2008). "Structural requirements for PCSK9-mediated degradation of the low-density lipoprotein receptor". Proceedings of the National Academy of Sciences of the United States of America. 105 (35): 13045–50. Bibcode:2008PNAS..10513045Z. doi:10.1073/pnas.0806312105. PMC 2526098. PMID 18753623.
  17. ^ Betteridge DJ (February 2013). "Cardiovascular endocrinology in 2012: PCSK9-an exciting target for reducing LDL-cholesterol levels". Nature Reviews. Endocrinology. 9 (2): 76–8. doi:10.1038/nrendo.2012.254. PMID 23296165. S2CID 27839784.
  18. ^ Chen CC, Cheng KJ, Ko TP, Guo RT (2015-01-09). "Current Progresses in Phytase Research: Three-Dimensional Structure and Protein Engineering". ChemBioEng Reviews. 2 (2): 76–86. doi:10.1002/cben.201400026.
  19. ^ Kopec KO, Lupas AN (2013). "β-Propeller blades as ancestral peptides in protein evolution". PLOS ONE. 8 (10): e77074. Bibcode:2013PLoSO...877074K. doi:10.1371/journal.pone.0077074. PMC 3797127. PMID 24143202.

Further reading

  • Branden C, Tooze J. (1999). Introduction to Protein Structure 2nd ed. Garland Publishing: New York, NY.

External links

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This is the Wikipedia entry entitled "WD40 repeat". More...

WD40 repeat Edit Wikipedia article

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:

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​; 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

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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

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Literature references

  1. Neer EJ, Schmidt CJ, Nambudripad R, Smith TF; , Nature 1994;371:297-300.: The ancient regulatory-protein family of WD-repeat proteins. PUBMED:8090199 EPMC:8090199


Internal database links

External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR001680

WD-40 repeats (also known as WD or beta-transducin repeats) are short ~40 amino acid motifs, often terminating in a Trp-Asp (W-D) dipeptide. WD40 repeats usually assume a 7-8 bladed beta-propeller fold, but proteins have been found with 4 to 16 repeated units, which also form a circularised beta-propeller structure. WD-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 and apoptosis. Repeated WD40 motifs act as a site for protein-protein or protein-DNA interaction, and proteins containing WD40 repeats are known to serve as platforms for the assembly of protein complexes or mediators of transient interplay among other proteins [ PUBMED:30069656 ]. 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 [ PUBMED:11814058 , PUBMED:10322433 ]. In Arabidopsis spp., several WD40-containing proteins act as key regulators of plant-specific developmental events.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan Beta_propeller (CL0186), which has the following description:

This large clan contains proteins that contain beta propellers. These are composed of between 6 and 8 repeats. The individual repeats are composed of a four stranded sheet. The clan includes families such as WD40 Pfam:PF00400 where the individual repeats are modeled. The clan also includes families where the entire propeller is modeled such as Pfam:PF02239 usually because the individual repeats are not discernible. These proteins carry out a very wide diversity of functions including catalysis.

The clan contains the following 112 members:

ANAPC1 ANAPC4_WD40 Arylesterase Arylsulfotran_2 Arylsulfotrans B_lectin BBS2_Mid BBS2_N Beta_propel Coatomer_WDAD CPSF_A CyRPA Cytochrom_D1 DCAF17 Dpp_8_9_N DPPIV_N DPPIV_rep DUF1513 DUF1668 DUF2415 DUF346 DUF3466 DUF3616 DUF3748 DUF4221 DUF4374 DUF4394 DUF4623 DUF4784 DUF4915 DUF4933 DUF4934 DUF5046 DUF5050 DUF5122 DUF5128 DUF5711 DUF839 eIF2A FG-GAP FG-GAP_2 FG-GAP_3 Frtz Ge1_WD40 Glu_cyclase_2 Glyoxal_oxid_N Gmad1 GSDH Helveticin_J HPS3_N HPS6 Hyd_WA IKI3 Itfg2 Kelch_1 Kelch_2 Kelch_3 Kelch_4 Kelch_5 Kelch_6 Lactonase Ldl_recept_b LGFP Lgl_C LVIVD Me-amine-dh_H MgpC MRJP Nbas_N NBCH_WD40 Neisseria_PilC NHL nos_propeller nos_propeller_2 Nucleoporin_N Nup160 Nup88 P1_N PALB2_WD40 PD40 Pectate_lyase22 Peptidase_S9_N PHTB1_N Phytase-like PQQ PQQ_2 PQQ_3 RAB3GAP2_N RAG2 RCC1 RCC1_2 Reg_prop RPE65 SBBP SBP56 SdiA-regulated Sema SGL SSL_N Str_synth TcdB_toxin_midN Tectonin TolB_like VID27 Vps16_N WD40 WD40_2 WD40_3 WD40_4 WD40_like WDCP YmzC

Alignments

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You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Pfam-B_2 (release 1.0)
Previous IDs: G-beta;
Type: Repeat
Sequence Ontology: SO:0001068
Author: Finn RD
Number in seed: 1465
Number in full: 938410
Average length of the domain: 39.40 aa
Average identity of full alignment: 24 %
Average coverage of the sequence by the domain: 18.77 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 61295632 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 27.0 12.1
Trusted cut-off 27.0 12.1
Noise cut-off 26.9 12.0
Model length: 38
Family (HMM) version: 35
Download: download the raw HMM for this family

Species distribution

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Colour assignments

Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
Viruses Viruses Unclassified Unclassified
Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Tree controls

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The tree shows the occurrence of this domain across different species. More...

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Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the WD40 domain has been found. There are 9287 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A096MJZ2 View 3D Structure Click here
A0A096Q886 View 3D Structure Click here
A0A096UWG1 View 3D Structure Click here
A0A0B4J2E5 View 3D Structure Click here
A0A0B4KEJ7 View 3D Structure Click here
A0A0G2JT65 View 3D Structure Click here
A0A0G2JVE0 View 3D Structure Click here
A0A0G2JVF8 View 3D Structure Click here
A0A0G2JWP6 View 3D Structure Click here
A0A0G2JY24 View 3D Structure Click here
A0A0G2JZL6 View 3D Structure Click here
A0A0G2K063 View 3D Structure Click here
A0A0G2K0C5 View 3D Structure Click here
A0A0G2K0H6 View 3D Structure Click here
A0A0G2K0P9 View 3D Structure Click here
A0A0G2K2B7 View 3D Structure Click here
A0A0G2K2Z0 View 3D Structure Click here
A0A0G2K3L8 View 3D Structure Click here
A0A0G2K4H2 View 3D Structure Click here
A0A0G2K679 View 3D Structure Click here
A0A0G2K7Z2 View 3D Structure Click here
A0A0G2K8S4 View 3D Structure Click here
A0A0G2K9A7 View 3D Structure Click here
A0A0G2K9U6 View 3D Structure Click here
A0A0G2KAW5 View 3D Structure Click here
A0A0G2KV24 View 3D Structure Click here
A0A0G2L107 View 3D Structure Click here
A0A0G2QC56 View 3D Structure Click here
A0A0G2QC64 View 3D Structure Click here
A0A0N4SUK7 View 3D Structure Click here
A0A0N7KG92 View 3D Structure Click here
A0A0P0UYZ4 View 3D Structure Click here
A0A0P0V0F4 View 3D Structure Click here
A0A0P0V0J2 View 3D Structure Click here
A0A0P0V1T8 View 3D Structure Click here
A0A0P0V3Y8 View 3D Structure Click here
A0A0P0V4C5 View 3D Structure Click here
A0A0P0V4X3 View 3D Structure Click here
A0A0P0V520 View 3D Structure Click here
A0A0P0V8T8 View 3D Structure Click here