WD-repeat
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The WD40 repeat (also known as the WD or beta-transducin repeat) is a short
structural motif In a chain-like biological molecule, such as a protein or nucleic acid, a structural motif is a common three-dimensional structure that appears in a variety of different, evolutionarily unrelated molecules. A structural motif does not have t ...
of approximately 40
amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...
s, often terminating in a
tryptophan Tryptophan (symbol Trp or W) is an α-amino acid that is used in the biosynthesis of proteins. Tryptophan contains an α-amino group, an α-carboxylic acid group, and a side chain indole, making it a polar molecule with a non-polar aromat ...
-
aspartic acid Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. The L-isomer of aspartic acid is one of the 22 proteinogenic amino acids, i.e., the building blocks of protei ...
(W-D) dipeptide. Tandem copies of these repeats typically fold together to form a type of circular
solenoid protein domain Solenoid protein domains are a highly modular type of protein domain. They consist of a chain of nearly identical Protein structure, folds, often simply called Protein tandem repeats, tandem repeats. They are extremely common among all types of pr ...
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 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- ...
structure (see figure to the right). 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
eukaryote The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...
s and are implicated in a variety of functions ranging from
signal transduction Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a biochemical cascade, series of molecular events. Proteins responsible for detecting stimuli are generally termed receptor (biology), rece ...
and
transcription regulation In molecular biology and genetics, transcriptional regulation is the means by which a cell regulates the conversion of DNA to RNA ( transcription), thereby orchestrating gene activity. A single gene can be regulated in a range of ways, from alt ...
to
cell cycle The cell cycle, or cell-division cycle, is the sequential series of events that take place in a cell (biology), cell that causes it to divide into two daughter cells. These events include the growth of the cell, duplication of its DNA (DNA re ...
control,
autophagy Autophagy (or autophagocytosis; from the Greek language, Greek , , meaning "self-devouring" and , , meaning "hollow") is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-depe ...
and
apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...
. The underlying common function of all WD40-repeat proteins is coordinating multi-protein complex assemblies, where the repeating units serve as a rigid
scaffold Scaffolding, also called scaffold or staging, is a temporary structure used to support a work crew and materials to aid in the construction, maintenance and repair of buildings, bridges and all other human-made structures. Scaffolds are widely u ...
for protein interactions. The specificity of the proteins is determined by the sequences outside the repeats themselves. Examples of such complexes are
G protein G proteins, also known as guanine nucleotide-binding proteins, are a Protein family, family of proteins that act as molecular switches inside cells, and are involved in transmitting signals from a variety of stimuli outside a cell (biology), ...
s (beta subunit is a beta-propeller), TAFII transcription factor, and
E3 ubiquitin ligase A ubiquitin ligase (also called an E3 ubiquitin ligase) is a protein that recruits an E2 ubiquitin-conjugating enzyme that has been loaded with ubiquitin, recognizes a protein substrate, and assists or directly catalyzes the transfer of ubiquitin ...
.


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 The Abelson helper integration site 1 (AHI1) is a protein coding gene that is known for the critical role it plays in brain development. Proper cerebellar and cortical development in the human brain depends heavily on AHI1. The AHI1 gene is prom ...
,
AMBRA1 AMBRA1 (activating molecule in Beclin1-regulated autophagy) is a protein that is able to regulate cancer cells through autophagy. AMBRA1 is described as a mechanism cells use to divide and there is new evidence demonstrating the role and impact o ...
,
APAF1 Apoptotic protease activating factor 1, also known as APAF1, is a human homolog of ''C. elegans'' CED-4 gene. Function The protein was identified in the laboratory of Xiaodong Wang as an activator of caspase-3 in the presence of cytochromeC a ...
,
ARPC1A Actin-related protein 2/3 complex subunit 1A is a protein that in humans is encoded by the ''ARPC1A'' gene. This gene encodes one of seven subunits of the human Arp2/3 protein complex. This subunit is a member of the SOP2 family of proteins and ...
,
ARPC1B Actin-related protein 2/3 complex subunit 1B is a protein that in humans is encoded by the ''ARPC1B'' gene. Function This gene encodes one of seven subunits of the human Arp2/3 protein complex. This subunit is a member of the SOP2 family of p ...
,
ATG16L1 Autophagy related 16 like 1 is a protein that in humans is encoded by the ''ATG16L1'' gene. This protein is characterized as a subunit of the autophagy-related ATG12- ATG5/ATG16 complex and is essentially important for the LC3 ( ATG8) lipidation ...
, *
BOP1 Ribosome biogenesis protein BOP1 is a protein that in humans is encoded by the ''BOP1'' gene. It is a WD40 repeat-containing nucleolar protein involved in rRNA processing, thereby controlling the cell cycle. It is required for the maturation o ...
,
BRWD1 Bromodomain and WD repeat-containing protein 1 (BRWD1) also known as WD repeat-containing protein 9 (WDR9) is a protein that in humans is encoded by the ''BRWD1'' gene. Function This gene encodes a member of the WD repeat protein family. WD re ...
, BRWD3, BTRC,
BUB3 Mitotic checkpoint protein BUB3 is a protein that in humans is encoded by the ''BUB3'' gene. Bub3 is a protein involved with the regulation of the Spindle Assembly Checkpoint (SAC); though BUB3 is non-essential in yeast, it is essential in highe ...
, * C6orf11,
CDC20 The cell division cycle protein 20 homolog is an essential regulator of cell division that is encoded by the ''CDC20'' gene in humans. To the best of current knowledge its most important function is to activate the anaphase promoting complex (AP ...
, CDC40, CDRT1, CHAF1B, CIAO1, CIRH1A,
COPA Copa or COPA may refer to: COPA COPA may refer to: * Child Online Protection Act, a former U.S. law to protect minors from certain material on the internet * Canadian Owners and Pilots Association * Cirrus Aircraft, Cirrus Owners and Pilots Asso ...
,
COPB2 Coatomer subunit beta is a protein that is encoded by the ''COPB2'' gene in humans. Function The Golgi coatomer complex (see MIM 601924) constitutes the coat of non-clathrin-coated vesicles and is essential for Golgi budding and vesicular traf ...
, CORO1A, CORO1B, CORO1C, CORO2A, CORO2B, CORO6, CORO7, CSTF1, *
DDB2 DNA damage-binding protein 2 is a protein that in humans is encoded by the ''DDB2'' gene. Structure As indicated by Rapić-Otrin et al. in 2003, the ''DDB2'' gene is located on human chromosome 11p11.2, spans a region of approximately 24 – 26 ...
, DENND3, DMWD, DMXL1, DMXL2, DNAI1, DNAI2, DNCI1, DTL,
DYNC1I1 Cytoplasmic dynein 1 intermediate chain 1 is a protein that in humans is encoded by the ''DYNC1I1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleot ...
,
DYNC1I2 Cytoplasmic dynein 1 intermediate chain 2 is a protein that in humans is encoded by the ''DYNC1I2'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleot ...
, EDC4, * EED, EIF3S2,
ELP2 Elongator complex protein 2 is a protein that in humans is encoded by the ''ELP2'' gene. Interactions ELP2 has been shown to interact with STAT3 and Janus kinase 1 Janus kinase 1 (JAK1) is a human tyrosine kinase protein essential for signal ...
,
EML1 Echinoderm microtubule-associated protein-like 1 is a protein that in humans is encoded by the ''EML1'' gene. Human echinoderm microtubule-associated protein-like is a strong candidate for the Usher syndrome type 1A gene. Usher syndromes (USHs) ...
, EML2, EML3, EML4, EML4-ALK, EML5, ERCC8, * FBXW10, FBXW11, FBXW2, FBXW4, FBXW5, FBXW7, FBXW8, FBXW9,
FZR1 Fizzy-related protein homolog, also known as hCDH1, is a protein that in humans is encoded by the ''FZR1'' gene. Interactions FZR1 has been shown to interact with CDC27 and FBXO5 F-box only protein 5 is a protein that in humans is encoded ...
, * GBL,
GEMIN5 Gem-associated protein 5 is a protein that in humans is encoded by the ''GEMIN5'' gene. Function Gem-associated protein 5 is part of the survival of motor neuron protein, SMN a large protein complex localized to both the cytoplasm and the cell ...
, GNB1, GNB1L, GNB2,
GNB2L1 Receptor for activated C kinase 1 (RACK1), also known as guanine nucleotide-binding protein subunit beta-2-like 1 (GNB2L1), is a 35 kDa protein that in humans is encoded by the RACK1 gene. Function RACK1 was originally isolated and identified ...
,
GNB3 Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 is a protein that in humans is encoded by the ''GNB3'' gene. Heterotrimeric guanine nucleotide-binding proteins ( G proteins), which integrate signals between receptors and eff ...
, GNB4,
GNB5 Guanine nucleotide-binding protein subunit beta-5 is a protein that in humans is encoded by the ''GNB5'' gene. Alternatively spliced transcript variants encoding different isoforms exist. Function Heterotrimeric guanine nucleotide-binding pro ...
, GRWD1, GTF3C2, * HERC1, HIRA, HZGJ, * IFT121, IFT122, IFT140, IFT172, IFT80, IQWD1, *
KATNB1 Katanin p80 WD40-containing subunit B1 is a protein that in humans is encoded by the ''KATNB1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides ...
, KIAA1336, KIF21A, KIF21B, KM-PA-2, *
KEAP1 Kelch-like ECH-associated protein 1 is a protein that in humans is encoded by the ''Keap1'' gene. Structure Keap1 has four discrete protein domains. The N-terminal Broad complex, Tramtrack and Bric-à-Brac (BTB) domain contains the Cys151 re ...
, * LLGL1, LLGL2, LRBA, LRRK1, LRRK2, LRWD1,
LYST Lysosomal trafficking regulator is a vesicular transport protein associated with Chédiak–Higashi syndrome. In melanocytic cells ''LYST'' gene expression may be regulated by MITF. References External links GeneReviews/NCBI/NIH/UW entry o ...
, * MAPKBP1, MED16, MORG1, * NBEA, NBEAL1,
NEDD1 Neural precursor cell expressed, developmentally down-regulated 1, also known as Nedd1, is a human gene and encodes the protein NEDD1. NEDD1 is localized in the centrosome and it plays a role in mitosis through its interaction with γ-tubulin. ...
, NLE1, NSMAF,
NUP37 Nucleoporin 37 (Nup37) is a protein that in humans is encoded by the ''NUP37'' gene. Function Transport of macromolecules between the cytoplasm and nucleus occurs through nuclear pore complexes (NPCs) embedded in the nuclear envelope The nucle ...
, NUP43, NWD1, * PAAF1,
PAFAH1B1 Platelet-activating factor acetylhydrolase IB subunit alpha or Lisencephaly protein-1 (LIS-1) is an enzyme that in humans is encoded by the ''PAFAH1B1'' gene. The protein plays an important role in regulating the motor protein dynein. Function ...
, PAK1IP1, PEX7, PHIP,
PIK3R4 Phosphoinositide 3-kinase regulatory subunit 4, also known as PI3-kinase regulatory subunit 4 or PI3-kinase p150 subunit or phosphoinositide 3-kinase adaptor protein, or ''VPS15'' is an enzyme that in humans is encoded by the ''PIK3R4'' gene ...
, PLAA, PLRG1,
PPP2R2A Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B alpha isoform is an enzyme regulator that in humans is encoded by the ''PPP2R2A'' gene. Function The product of this gene belongs to the phosphatase 2 regulatory subunit B fa ...
, PPP2R2B, PPP2R2C, PPP2R2D, PPWD1, PREB, PRPF19, PRPF4,
PWP1 Periodic tryptophan protein 1 homolog is a protein that in humans is encoded by the ''PWP1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides i ...
, PWP2, *
RAE1 mRNA export factor is a protein that in humans is encoded by the ''RAE1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transc ...
, RPTOR,
RBBP4 Histone-binding protein RBBP4 (also known as RbAp48, or NURF55) is a protein that in humans is encoded by the ''RBBP4'' gene. Function This gene encodes a ubiquitously expressed nuclear protein that belongs to a highly conserved subfamily of ...
, RBBP5,
RBBP7 Histone-binding protein RBBP7 is a protein that in humans is encoded by the ''RBBP7'' gene. Function This protein is a ubiquitously expressed nuclear protein and belongs to a highly conserved subfamily of WD-repeat proteins. It is found amon ...
, RFWD2, RFWD3,
RRP9 U3 small nucleolar RNA-interacting protein 2 is a protein that in humans is encoded by the ''RRP9'' gene. See also * Fibrillarin * Small nucleolar RNA U3 * RCL1 * RRP9 * UTP6 * UTP11L * UTP14A * UTP15 U3 small nucleolar RNA-associated p ...
, *
SCAP SCAP may refer to: * S.C.A.P., an early French manufacturer of cars and engines * Security Content Automation Protocol * '' The Shackled City Adventure Path'', a role-playing game * SREBP cleavage activating protein * Supervisory Capital Assessm ...
, SEC13, SEC31A, SEC31B, SEH1L, SHKBP1, SMU1, SPAG16, SPG,
STRAP A strap, sometimes also called strop, is an elongated flap or ribbon, usually of leather or other flexible materials. Thin straps are used as part of clothing or baggage, or bedding such as a sleeping bag. See for example spaghetti strap, s ...
,
STRN Striatin is a protein that in humans is encoded by the ''STRN'' gene. Interactions STRN has been shown to interact with: * CTTNBP2NL, * CTTNBP2, * FAM40A, * MOBKL3, * PDCD10, * PPP2CA, * PPP2R1A, * RP6-213H19.1, * STK24, * S ...
, STRN3, STRN4,
STXBP5 Syntaxin-binding protein 5 is a protein that in humans is encoded by the ''STXBP5'' gene. It is also known as tomosyn, after , "friend" in Japanese, for its role as a binding protein. Function Syntaxin 1 is a component of the 7S and 20S SNARE ...
, STXBP5L, * TAF5, TAF5L, TBL1X, TBL1XR1, TBL1Y, TBL2, TBL3,
TEP1 Telomerase protein component 1 is an enzyme that in humans is encoded by the ''TEP1'' gene. Function This gene product is a component of the ribonucleoprotein complex responsible for telomerase activity which catalyzes the addition of new te ...
, THOC3, THOC6,
TLE1 Transducin-like enhancer protein 1 is a protein that in humans is encoded by the ''TLE1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DN ...
,
TLE2 Transducin-like enhancer protein 2 is a protein that in humans is encoded by the ''TLE2'' gene. Interactions TLE2 has been shown to interact with TLE1 Transducin-like enhancer protein 1 is a protein that in humans is encoded by the ''TLE1'' ge ...
, TLE3, TLE4, TLE6, TRAF7, TSSC1, TULP4, TUWD12, *
UTP15 U3 small nucleolar RNA-associated protein 15 homolog is a protein that in humans is encoded by the ''UTP15'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence o ...
, UTP18, * WAIT1, WDF3, WDFY1, WDFY2, WDFY3, WDFY4, WDHD1, WDR1, WDR10, WDR11, WDR12, WDR13, WDR16, WDR17, WDR18, WDR19, WDR20, WDR21A, WDR21C, WDR22, WDR23,
WDR24 WD repeat-containing protein 24 is a protein that in humans is encoded by the ''WDR24'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA ...
, 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 WD repeat domain 57 (U5 snRNP specific), also known as WDR57, is a gene found in many organisms, including, but not limited to Homo sapiens, Gallus gallus, Pan troglodytes, Canus familiaris, Bos taurus, Mus musculus, and Rattus norvegicus. Fun ...
, WDR59, WDR5B, WDR6, WDR60, WDR61, WDR62, WDR63, WDR64, WDR65, WDR66, WDR67,
WDR68 WD repeat-containing protein 68 is a protein that in humans is encoded by the ''DCAF7'' gene. Interactions WDR68 has been shown to interact with DYRK1A Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in huma ...
, 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 WD repeat and SOCS box-containing protein 1 is a protein that in humans is encoded by the ''WSB1'' gene. This gene encodes a member of the WD-protein subfamily. This protein shares a high sequence identity to mouse and chick proteins. It contain ...
, WSB2, * ZFP106


See also

*
Beta-propeller 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- ...
* Tomosyn, a protein two WD40 domains *
Protein tandem repeats An array of protein tandem repeats is defined as several (at least two) adjacent copies having the same or similar sequence motifs. These periodic sequences are generated by internal duplications in both coding and non-coding genomic sequences. Re ...


References


External links

* * * * * * * * * * * * * * * * * {{InterPro content, IPR001680